Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 663
Filtrar
1.
Cancer Sci ; 111(1): 200-208, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31778288

RESUMO

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11ß1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non-small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT-PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence-free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Cadeias alfa de Integrinas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
PLoS One ; 14(12): e0224610, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31869339

RESUMO

Malaria is an infectious disease of major worldwide clinical importance that causes a variety of severe, or complicated, syndromes including cerebral malaria, which is often fatal. Leukocyte integrins are essential for host defense but also mediate physiologic responses of the innate and adaptive immune systems. We previously showed that targeted deletion of the αD subunit (αD-/-) of the αDß2 integrin, which is expressed on key leukocyte subsets in mice and humans, leads to absent expression of the integrin heterodimer on murine macrophages and reduces mortality in mice infected with Plasmodium berghei ANKA (P. berghei ANKA). To further identify mechanisms involved in the protective effect of αD deletion in this model of severe malaria we examined wild type C57BL/6 (WT) and αD-/- mice after P. berghei ANKA infection and found that vessel plugging and leukocyte infiltration were significantly decreased in the brains of αD-/- animals. Intravital microscopy demonstrated decreased rolling and adhesion of leukocytes in cerebral vessels of αD-/- mice. Flow cytometry analysis showed decreased T-lymphocyte accumulation in the brains of infected αD-/- animals. Evans blue dye exclusion assays demonstrated significantly less dye extravasation in the brains of αD-/- mice, indicating preserved blood-brain barrier integrity. WT mice that were salvaged from P. berghei ANKA infection by treatment with chloroquine had impaired aversive memory, which was not observed in αD-/- mice. We conclude that deletion of integrin αDß2 alters the natural course of experimental severe malaria, demonstrating previously unrecognized activities of a key leukocyte integrin in immune-inflammatory responses that mediate cerebral involvement.


Assuntos
Antígenos CD11/metabolismo , Cadeias alfa de Integrinas/metabolismo , Malária/fisiopatologia , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Edema Encefálico/metabolismo , Edema Encefálico/fisiopatologia , Antígenos CD11/fisiologia , Cloroquina/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , Cadeias alfa de Integrinas/fisiologia , Integrinas/imunologia , Integrinas/metabolismo , Contagem de Leucócitos , Leucócitos/metabolismo , Leucócitos/fisiologia , Macrófagos/metabolismo , Malária/genética , Malária Cerebral/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Plasmodium berghei/metabolismo
3.
BMC Infect Dis ; 19(1): 999, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775660

RESUMO

BACKGROUND: Recent studies have shown that CD103 is an important marker for tissue-resident memory T cells (TRM) which plays an important role in anti-infection. However, the role of CD103+ TRM was not elucidated in the progress of S. japonicum infection induced disease. METHODS: 6-8 weeks old C57BL/6 mice were infected by S. japonicum. Mice were sacrificed and the lungs were removed 5-6 weeks after infection. Immunofluorescent staining and Q-PCR were performed to identify the expression of CD103 molecule. Single cellular populations were made, percentages of CD103 on both CD4+ and CD8+ T lymphocytes were dynamical observed by flow cytometry (FCM). Moreover, the expression of memory T cells related molecules CD69 and CD62L, T cell function associated molecules CD107a, IFN-γ, IL-4, IL-9, and IL-10 were compared between CD103+ CD4+ and CD8+ T cells by FCM. RESULTS: CD103+ cells were emerged in the lung of both naive and S. japonicum infected mice. Both the percentage and the absolute numbers of pulmonary CD4+ and CD8+ cells were increased after S. japonicum infection (P < 0.05). The percentage of CD103+ cells in CD8+ T cells decreased significantly at the early stage of S. japonicum infection (P < 0.05). Increased CD69, decreased CD62L and CD107a expressions were detected on both CD4+ and CD8+ CD103+ T cells in the lungs of infected mice (P < 0.05). Compared to CD8+ CD103+ T cells, CD4+ CD103+ T cells from infected mice expressed higher level of CD69 and lower level CD62L molecules (P < 0.05). Moreover, higher percentage of IL-4+, IL-9+ and IL-10+ cells on CD4+ CD103+ pulmonary T cells was found in infected mice (P < 0.05). Significantly increased IL-4 and IL-9, and decreased IFN-γ expressing cells were detected in CD8+CD103+ cells of infected mice (P < 0.05). CONCLUSIONS: CD103-expressing pulmonary CD4+ and CD8+ T cells play important roles in mediating S. japonicum infection induced granulomatous inflammation in the lung.


Assuntos
Antígenos CD/genética , Antígenos CD/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Cadeias alfa de Integrinas/genética , Cadeias alfa de Integrinas/metabolismo , Schistosoma japonicum , Esquistossomose Japônica/metabolismo , Animais , Biomarcadores/metabolismo , Citocinas/metabolismo , Feminino , Expressão Gênica/imunologia , Memória Imunológica , Pulmão/metabolismo , Pulmão/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Esquistossomose Japônica/microbiologia
4.
Nat Immunol ; 20(11): 1469-1480, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31591568

RESUMO

Tissue-resident memory T cells (TRM cells) are crucial mediators of adaptive immunity in nonlymphoid tissues. However, the functional heterogeneity and pathogenic roles of CD4+ TRM cells that reside within chronic inflammatory lesions remain unknown. We found that CD69hiCD103lo CD4+ TRM cells produced effector cytokines and promoted the inflammation and fibrotic responses induced by chronic exposure to Aspergillus fumigatus. Simultaneously, immunosuppressive CD69hiCD103hiFoxp3+ CD4+ regulatory T cells were induced and constrained the ability of pathogenic CD103lo TRM cells to cause fibrosis. Thus, lung tissue-resident CD4+ T cells play crucial roles in the pathology of chronic lung inflammation, and CD103 expression defines pathogenic effector and immunosuppressive tissue-resident cell subpopulations in the inflamed lung.


Assuntos
Comunicação Celular/imunologia , Tolerância Imunológica , Memória Imunológica , Fibrose Pulmonar/imunologia , Linfócitos T Reguladores/imunologia , Animais , Antígenos CD/metabolismo , Antígenos de Fungos/imunologia , Aspergillus fumigatus/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Cadeias alfa de Integrinas/metabolismo , Pulmão/citologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos Transgênicos , Fibrose Pulmonar/patologia , Linfócitos T Reguladores/metabolismo
5.
Biomed Pharmacother ; 118: 109031, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545219

RESUMO

BACKGROUND: This study was conducted to investigate the protective effect of Fms-like tyrosine kinase 3 (FLT3)/FLT3 ligand (FLT3L)-dependent CD103+ dendritic cells (DCs) on hepatic ischemia-reperfusion injury (IRI). METHODS: A mouse model of hepatic IRI and cellular model following hypoxia-reperfusion (H/R) treatment were established. Peripheral blood and liver tissues were obtained and analyzed by flow cytometer in terms of percentage of CD103+DCs and regulatory T (Treg) cells. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were determined to assess liver function. Moreover, pro-inflammatory cytokines levels including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). The histological morphology of liver tissues was examined with hematoxylin and eosin (HE) staining. The apoptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP Nick End Labeling (TUNEL) assay. Treg-associated cytokines transforming growth factor (TGF)-ß and IL-10 expressions were measured using quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: CD103+ DCs were significantly decreased in peripheral blood and liver tissues of mouse model of hepatic IRI. In vivo experiments indicated that CD103+ DCs infusion ameliorated IRI-induced liver damage and Treg inhibition. Further investigations demonstrated that FLT3/FLT3L-dependent CD103+ DCs suppressed hepatocyte apoptosis via activation of Treg cells in vitro. CONCLUSION: FLT3/FLT3L-induced CD103+ DCs alleviated hepatic IRI through activating Treg cells.


Assuntos
Antígenos CD/metabolismo , Células Dendríticas/transplante , Cadeias alfa de Integrinas/metabolismo , Fígado/irrigação sanguínea , Proteínas de Membrana/metabolismo , Traumatismo por Reperfusão/terapia , Linfócitos T Reguladores/imunologia , Tirosina Quinase 3 Semelhante a fms/metabolismo , Animais , Transplante de Células , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Fígado/imunologia , Testes de Função Hepática , Ativação Linfocitária , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/imunologia
6.
Drug Dev Res ; 80(8): 1080-1088, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31411346

RESUMO

Paclitaxel (PTX) is a chemotherapeutic agent which shows antitumor activities against a broad spectrum of cancers. Yet, the current formulation of PTX used in clinic may cause a number of adverse reactions, which significantly limit its application. To obtain better clinical use of PTX, we report, for the first time, iRGD-PTX conjugate nanoparticles (NPs) for targeted PTX delivery. iRGD-PTX conjugate was synthesized from thiolated iRGD and 6-maleimidocaproic acid-PTX through Michael addition reaction. iRGD-PTX NPs with hydrodynamic diameter of ~110 nm were self-assembled from iRGD-PTX conjugate in deionized water. The as-prepared iRGD-PTX NPs exhibit good stability in phosphate buffered saline (PBS) buffer and fetal bovine serum containing PBS buffer. iRGD-PTX NPs exhibit sustained drug release behaviors. The in vitro studies show that iRGD-PTX NPs can be internalized by 4T1 cells by integrin αV-mediated endocytosis, resulting in better in vitro antitumor activity as compared to free PTX. The in vivo studies demonstrate that iRGD-PTX NPs exhibit enhanced tumor accumulation. The iRGD-PTX NPs reported here represent a novel PTX nanoplatform to achieve targeted PTX delivery.


Assuntos
Cadeias alfa de Integrinas/metabolismo , Neoplasias/metabolismo , Oligopeptídeos/química , Paclitaxel/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Estabilidade de Medicamentos , Endocitose , Humanos , Células MCF-7 , Camundongos , Nanopartículas , Neoplasias/tratamento farmacológico , Paclitaxel/química , Tamanho da Partícula
7.
Molecules ; 24(16)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31408997

RESUMO

One of the crucial aspects of screening antisense oligonucleotides destined for therapeutic application is confidence that the antisense oligomer is delivered efficiently into cultured cells. Efficient delivery is particularly vital for antisense phosphorodiamidate morpholino oligomers, which have a neutral backbone, and are known to show poor gymnotic uptake. Here, we report several methods to deliver these oligomers into cultured cells. Although 4D-Nucleofector™ or Neon™ electroporation systems provide efficient delivery and use lower amounts of phosphorodiamidate morpholino oligomer, both systems are costly. We show that some readily available transfection reagents can be used to deliver phosphorodiamidate morpholino oligomers as efficiently as the electroporation systems. Among the transfection reagents tested, we recommend Lipofectamine 3000™ for delivering phosphorodiamidate morpholino oligomers into fibroblasts and Lipofectamine 3000™ or Lipofectamine 2000™ for myoblasts/myotubes. We also provide optimal programs for nucleofection into various cell lines using the P3 Primary Cell 4D-Nucleofector™ X Kit (Lonza), as well as antisense oligomers that redirect expression of ubiquitously expressed genes that may be used as positive treatments for human and murine cell transfections.


Assuntos
Eletroporação/métodos , Morfolinos/genética , Oligonucleotídeos Antissenso/genética , Interferência de RNA , Transfecção/métodos , Animais , Linhagem Celular , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Cadeias alfa de Integrinas/antagonistas & inibidores , Cadeias alfa de Integrinas/genética , Cadeias alfa de Integrinas/metabolismo , Lipídeos/química , Camundongos , Camundongos Endogâmicos mdx , Morfolinos/síntese química , Morfolinos/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Oligonucleotídeos Antissenso/síntese química , Oligonucleotídeos Antissenso/metabolismo , Cultura Primária de Células , Proteínas do Complexo SMN/antagonistas & inibidores , Proteínas do Complexo SMN/genética , Proteínas do Complexo SMN/metabolismo
8.
J Clin Lab Anal ; 33(8): e22973, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31418948

RESUMO

BACKGROUND: The present study aimed to evaluate the correlation of integrin alpha 7 (ITGA7) with patients' clinicopathological characteristics and survival profiles, as well as its influence on cell proliferation, apoptosis, and stemness in non-small-cell lung cancer (NSCLC). METHODS: A total of 397 NSCLC patients underwent surgical resection were included, and ITGA7 was measured in tumor tissues and adjacent tissues by immunohistochemistry. patients' clinical data were extracted from database, and follow-up records were reviewed. In cellular experiments, expression of ITGA7 was measured in NSCLC cell lines and normal human lung epithelial cell line by RT-qPCR. The influence of ITGA7 on cell activity was assessed by transfecting overexpression plasmids and knockdown plasmids of ITGA7 into A549 cells. RESULTS: Integrin alpha 7 was upregulated in tumor tissues compared with the adjacent tissues of NSCLC patients. Patients with ITGA7 high expression presented poorer pathological differentiation, larger tumor size, and more advanced TNM stage compared with patients with ITGA7 low expression. For survival profiles, both disease-free survival and overall survival were shorter in ITGA7 high expression patients compared with ITGA7 low expression patients. In cellular experiments, ITGA7 was upregulated in NCI-H1650, A549, HCC-827, and NCI-H1299 cells compared with normal human lung epithelial cells BEAS-2B. In addition, ITGA7 promoted cell proliferation, inhibited cell apoptosis, and facilitated cell stemness in A549 cells. CONCLUSION: Integrin alpha 7 correlates with poor clinicopathological characteristics and survival profiles, and it promotes cell proliferation, stemness but suppresses cell apoptosis in NSCLC.


Assuntos
Antígenos CD/metabolismo , Apoptose , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Proliferação de Células , Cadeias alfa de Integrinas/metabolismo , Neoplasias Pulmonares/mortalidade , Células-Tronco Neoplásicas/patologia , Células A549 , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Taxa de Sobrevida
9.
J Dermatol Sci ; 95(1): 21-27, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31300254

RESUMO

BACKGROUND: A number of studies have shown the relationship between the pathogenesis of psoriasis and skin resident memory T (TRM) cells. OBJECTIVE: To investigate the cytokine profile of TRM cells from skin lesions of psoriasis and the relationship of skin TRM cells to the future clinical course of psoriasis. METHODS: We used stocked samples of T cells that were ex vivo expanded from skin biopsies of 10 patients with psoriasis vulgaris. A half of 4-mm punch biopsy specimens was subjected to expansion of skin-infiltrating T cells using IL-2 and anti-CD3/CD28 antibody-coated microbeads. More than 106 T cells per specimen were stocked at -80°C. Defrosted cells were subjected to flow cytometric analysis. Another half of skin biopsies were subjected to immmunofluorescence staining for CD103 and other markers. RESULTS: The biopsied skin revealed CD8+CD103+ TRM cells were present in the epidermis of psoriasis and associated with acanthosis. Sorted CD103+ T cells were mostly CD8+ memory T cells expressing CD69 with a skin-homing potential. A part of CD8+CD103+ T cells produced interferon-γ, IL-17A or IL-22. Notably, CD8+CD103+ TRM cells more frequently produced IL-17A than did CD8+CD103- T cells. We retrospectively divided the 10 cases into the non-advanced therapy group, and the advanced therapy group in which systemic biologics or others were initiated within one year. The frequency of CD8+CD103+IL-17A+ TRM cells tended to be higher in the advanced therapy group. CONCLUSION: These results suggest that IL-17A-producing CD8+CD103+ TRM cells are associated with a progressive clinical course of psoriasis.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Memória Imunológica , Interleucina-17/metabolismo , Psoríase/imunologia , Adulto , Antígenos CD/metabolismo , Biópsia , Linfócitos T CD8-Positivos/metabolismo , Progressão da Doença , Feminino , Humanos , Cadeias alfa de Integrinas/metabolismo , Interleucina-17/imunologia , Masculino , Pessoa de Meia-Idade , Psoríase/patologia , Estudos Retrospectivos , Pele/citologia , Pele/imunologia , Pele/patologia
10.
Mucosal Immunol ; 12(5): 1118-1129, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31312028

RESUMO

The immune system of the cervicovaginal tract (CVT) must balance immunosurveillance and active immunity against pathogens with maintenance of tolerance to resident microbiota and to fetal and partner antigens for reproductive purposes. Thus, we predicted that CVT immunity is characterized by distinctive features compared to blood and other tissue compartments. Indeed, we found that CVT CD8+ T-cells had unique transcriptional profiles, particularly in their cytokine signature, compared to that reported for CD8+ T-cells in other tissue sites. Among these CVT CD8+ T-cells, we identified a CD69- CD103- subset that was characterized by reduced migration in response to tissue-exit signals and higher pro-inflammatory potential as compared to their blood counterpart. These inflammatory mucosal CD8+ T-cells (Tim) were increased in frequency in the CVT of individuals with chronic infection, pointing to a potential role in perpetuating inflammation. Our findings highlight the specialized nature of immunity within the CVT and identify Tim cells as potential therapeutic targets to tame tissue inflammation upon chronic infection.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Colo do Útero/imunologia , Colo do Útero/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Vagina/imunologia , Vagina/metabolismo , Adulto , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Biomarcadores , Citocinas/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Memória Imunológica , Imunofenotipagem , Mediadores da Inflamação/metabolismo , Cadeias alfa de Integrinas/metabolismo , Lectinas Tipo C/metabolismo , Ativação Linfocitária , Contagem de Linfócitos , Camundongos , Pessoa de Meia-Idade , Adulto Jovem
11.
Rheumatology (Oxford) ; 58(11): 2039-2050, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31329981

RESUMO

OBJECTIVES: We previously reported that ex vivo TGF-ß and IL-2-induced CD8+CD103+ regulatory T cells (CD8+CD103+ iTregs) displayed similar immunosuppressive effect and therapeutic function on lupus mice nephritis to that of CD4+Foxp3+ Tregs. In view of the important role of glomerular endothelial cell (GEC) injury in inflammatory processes in SLE, this study aimed to investigate the nature and mechanism of CD8+CD103+ iTregs-mediated amelioration of LN by attenuating GEC injury. METHODS: Treg cells from patients with SLE and from healthy controls were characterized by flow cytometry analysis. The expression of pro-inflammatory mediators and VEGF were analysed in healthy controls, patients with SLE and MRL/lpr mice by ELISA, western blot, and real-time quantitative RT-PCR (qRT-PCR). Typical lesions of diffuse proliferative LN were observed in MRL/lpr mice through the use of haematoxylin and eosin, Masson, periodic acid-Schiff, periodic acid-Schiff methenamine, transmission electron microscopy and IF microscopy. Angiogenesis was analysed in GECs by cell investigating proliferation, migration, and tube formation. RESULTS: The results revealed that the frequency of Treg cells was inversely correlated with the expression of VCAM-1 and ICAM-1 in patients with SLE. Furthermore, adoptive transfer of CD8+CD103+ iTregs to MRL/lpr mice was associated with decreased levels of autoantibodies and proteinuria, reduced renal pathological lesions, and lowered renal deposition of IgG/C3. We further found that CD8+CD103+ iTregs not only suppressed the expression of pro-inflammatory mediators but also attenuated GEC injury by promoting angiogenesis. CONCLUSION: Our study has identified the role of CD8+CD103+ iTregs on attenuating GEC injury and provided a possible application of this new iTregs subset in lupus nephritis and other autoimmune diseases.


Assuntos
Antígenos CD/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Células Endoteliais/imunologia , Cadeias alfa de Integrinas/metabolismo , Nefrite Lúpica/imunologia , Linfócitos T Reguladores/metabolismo , Transferência Adotiva , Animais , Autoanticorpos/imunologia , Progressão da Doença , Humanos , Molécula 1 de Adesão Intercelular/imunologia , Rim/imunologia , Glomérulos Renais/citologia , Camundongos , Camundongos Endogâmicos MRL lpr , Molécula 1 de Adesão de Célula Vascular/imunologia
12.
J Clin Lab Anal ; 33(8): e22979, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325216

RESUMO

BACKGROUND: This study aimed to investigate the correlation of integrin α7 (ITGA7) expression with clinical/pathological characteristics and overall survival (OS), and its knockdown on inhibiting cell activities in breast cancer. METHODS: A total of 191 breast cancer patients underwent surgery were retrospectively reviewed, and ITGA7 expression in tumor tissues was determined by immunofluorescence and real-time quantitative polymerase chain reaction. Patients' clinical/pathological data were recorded, and OS was calculated. In vitro, control shRNA and ITGA7 shRNA plasmids were transfected into MCF7 cells to evaluate the influence of ITGA7 knockdown on cell proliferation, apoptosis, and invasion. RESULTS: Ninety-two (48.2%) patients presented with ITGA7 high expression, and 99 patients (51.8%) presented with ITGA7 low expression. ITGA7 expression was positively correlated with T stage, tumor-node metastasis (TNM) stage, and pathological grade. Kaplan-Meier curves showed that ITGA7 high expression was associated with shorter OS, and multivariate Cox's proportional hazards regression displayed that ITGA7 high expression was an independent predictive factor for poor OS. Moreover, in vitro experiments disclosed that cell proliferation (by Cell Counting Kit-8 assay) and cell invasion (by Matrigel invasion assay) were reduced, while cell apoptosis rate (by Annexin V/propidium iodide assay) was enhanced by ITGA7 knockdown in MCF-7 cells. CONCLUSION: Integrin α7 high expression correlates with increased T stage, TNM stage, and pathological grade as well as worse OS, and its knockdown enhances cell apoptosis but inhibits cell proliferation and invasion in breast cancer.


Assuntos
Antígenos CD/metabolismo , Apoptose , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/mortalidade , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Cadeias alfa de Integrinas/metabolismo , Antígenos CD/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Cadeias alfa de Integrinas/antagonistas & inibidores , Cadeias alfa de Integrinas/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , RNA Interferente Pequeno/genética , Estudos Retrospectivos , Taxa de Sobrevida
13.
Acta Histochem ; 121(5): 657-663, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31153587

RESUMO

The prognostic significance and clinical implications of resident CD103+CD8+T cells in human colorectal cancer tissues still remains largely unexplored. In our present study, we aimed to characterize the resident CD8+T cells in human colorectal cancer tissues by using double staining of CD103 and CD8, and further evaluated the prognostic significance of resident CD8+T cells in colorectal cancer. We found that the OS rate of the colorectal cancer patients with higher infiltration of CD8+T cells, or with higher numbers of resident CD103+CD8+T cells, or with higher ratio of CD103+CD8+T cells over total CD8+T cells in cancer tissues was significantly better than that of the patients with lower infiltration of CD8+T cells, or with lower numbers of resident CD103+CD8+T cells, or with higher ratio of CD103+CD8+T cells over total CD8+T cells in cancer tissues, respectively. Moreover, higher infiltration of CD8+T cells in colorectal cancer tissues was significantly and inversely correlated with advanced TNM stage. Higher numbers of resident CD103+CD8+T cells in colorectal cancer tissues were significantly and inversely correlated with distant metastasis status. Higher ratio of CD103+CD8+T cells over total CD8+T cells in colorectal cancer tissues was significantly and inversely correlated with age status. The COX model analysis demonstrated that higher infiltration of CD8+T cells, higher numbers of resident CD103+CD8+T cells, or higher ratio of CD103+CD8+T cells over total CD8+T cells in colorectal cancer tissues, could serve as independent prognostic predictors for colorectal cancer patients. Taken together, our present study demonstrated the density of tumor infiltrating CD8+T cells or the numbers of resident CD103+CD8+T cells in colorectal tissues could be used as an important prognostic predictor for this malignancy.


Assuntos
Antígenos CD/análise , Linfócitos T CD8-Positivos , Neoplasias Colorretais/mortalidade , Cadeias alfa de Integrinas/análise , Linfócitos do Interstício Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Antígenos CD8/metabolismo , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Cadeias alfa de Integrinas/metabolismo , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Subpopulações de Linfócitos T
14.
Mol Med Rep ; 19(6): 5377-5385, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059096

RESUMO

Hyperglycemia promotes the growth and reproduction of bacteria, thereby increasing the probability of infection, which also causes rebound hyperglycemia. Therefore, the interactions of infection and hyperglycemia lead to the progression and deterioration of these diseases. Type 1 diabetes mellitus (T1DM) is an autoimmune disease. Studies have shown that regulatory T cells (Tregs) play a key role in maintaining islet­specific tolerance. Treg deficiency may lead to the development of early pancreatitis and T1DM, and sufficient amounts of Tregs can restore this tolerance, thereby inhibiting the occurrence of T1DM. Moreover, different subpopulations of dendritic cells (DCs) play an important role in activating autoreactive T cells and inducing autoimmune tolerance to autoantigens, which are closely related to the functional diversity caused by different phenotypes, maturation status, and the immune microenvironment of DC subpopulations. In the present study, we used streptozotocin­induced hyperglycemic mice to model T1DM and induced a Salmonella infection in the mouse model, leading to aggravated inflammation, which resulted in an elevated proportion of CD103+CD11b+ DCs and a significantly elevated proportion of CD4+FoxP3+ Tregs in the intestinal lamina propria. After co­culturing CD4+ T cells and DCs, we found that CD103+CD11b+ DCs could significantly promote the proliferation of CD4+ T cells. The elevated proportions of CD4+FoxP3+ Tregs were considered to be correlated with the increased number of CD103+CD11b+ DCs.


Assuntos
Infecções por Salmonella/patologia , Linfócitos T Reguladores/metabolismo , Animais , Antígenos CD/metabolismo , Antígeno CD11b/metabolismo , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/metabolismo , Técnicas de Cocultura , Citocinas/sangue , Células Dendríticas/citologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Feminino , Fatores de Transcrição Forkhead/metabolismo , Inflamação , Cadeias alfa de Integrinas/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas/patologia , Salmonella/patogenicidade , Infecções por Salmonella/imunologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia
15.
Mol Cancer ; 18(1): 86, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975145

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (CCRCC) is characterized by a highly metastatic potential. The stromal communication between stem cells and cancer cells critically influences metastatic dissemination of cancer cells. METHODS: The effect of exosomes isolated from cancer stem cells (CSCs) of CCRCC patients on the progress of epithelial-mesenchymal transition (EMT) and lung metastasis of CCRCC cells were examined. RESULTS: CSCs exosomes promoted proliferation of CCRCC cells and accelerated the progress of EMT. Bioactive miR-19b-3p transmitted to cancer cells by CSC exosomes induced EMT via repressing the expression of PTEN. CSCs exosomes derived from CCRCC patients with lung metastasis produced the strongest promoting effect on EMT. Notably, CD103+ CSC exosomes were enriched in tumor cells and in lung as well, highlighting the organotropism conferred by CD103. In addition, CD103+ exosomes were increased in blood samples from CCRCC patients with lung metastasis. CONCLUSIONS: CSC exosomes transported miR-19b-3p into CCRCC cells and initiated EMT promoting metastasis. CD103+ acted to guide CSC exosomes to target cancer cells and organs, conferring the higher metastatic capacity of CCRCC to lungs, suggesting CD103+ exosomes as a potential metastatic diagnostic biomarker. ᅟ.


Assuntos
Antígenos CD/genética , Carcinoma de Células Renais/genética , Exossomos/metabolismo , Cadeias alfa de Integrinas/genética , Neoplasias Renais/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Animais , Antígenos CD/metabolismo , Transporte Biológico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/secundário , Comunicação Celular , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Exossomos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Cadeias alfa de Integrinas/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Metástase Linfática , Camundongos Nus , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , PTEN Fosfo-Hidrolase/metabolismo , Transdução de Sinais , Células Estromais/metabolismo , Células Estromais/patologia , Microambiente Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
16.
J Immunol Res ; 2019: 8575407, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30915372

RESUMO

Objective: To investigate the potential therapeutic effect in a rheumatoid arthritis model of stable human CD8+ regulatory T cells (hCD8+Tregs) induced by TGF-ß1 and rapamycin (RAPA) in vitro. Methods: Human CD8+T cells were isolated from human peripheral blood mononuclear cells and induced/expanded with TGF-ß1 and RAPA along with anti-CD3/28 beads and IL-2 in vitro and harvested as hCD8+Tregs. The phenotypes, suppressive characteristics, and stability of the hCD8+Tregs in an inflammatory microenvironment were examined in vitro. Human CD8+Tregs were transfused into an acollagen-induced arthritis (CIA) mouse model, and their therapeutic effects and related mechanisms were investigated. Results: Human CD8+Tregs induced by TGF-ß1/RAPA showed high expression of Foxp3 and CD103, exhibited vigorous suppression ability, and were stable in inflammatory microenvironments. In CIA mice, the clinical scores, levels of anti-collagen IgG antibody, and cartilage destruction were significantly reduced after adoptive transfusion with hCD8+Tregs. Moreover, hCD8+Treg treatment significantly reduced the number of Th17 cells, increased the number of CD4+IFN-γ +T cells, and produced self CD4+Foxp3+Tregs in vivo. In an in vitro cell coculture assay, hCD8+Tregs significantly inhibited mouse CD4+ effector T cell proliferation, induced mouse CD4+Foxp3+Treg and CD4+IFN-γ +Th1 cell production, reduced Th17 cell development, and downregulated CD80/86 expression on mature DCs (mDCs). Conclusion: TGF-ß1/RAPA can induce hCD8+Tregs with stable suppressive characteristics, which could significantly alleviate the severity of CIA based on their stable suppressive ability in an inflammatory microenvironment and further influence the function of other downstream cell subtypes. Human CD8+Tregs might be a therapeutic strategy for rheumatoid arthritis.


Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Imunoterapia/métodos , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Animais , Antígenos CD/metabolismo , Artrite Experimental/terapia , Artrite Reumatoide/terapia , Antígenos CD8/metabolismo , Células Cultivadas , Colágeno/imunologia , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunoglobulina G/metabolismo , Cadeias alfa de Integrinas/metabolismo , Camundongos , Camundongos Endogâmicos DBA , Tolerância a Antígenos Próprios , Sirolimo/farmacologia , Linfócitos T Reguladores/transplante , Fator de Crescimento Transformador beta/metabolismo
17.
Inflamm Bowel Dis ; 25(9): 1497-1509, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-30918941

RESUMO

BACKGROUND: The integrin CD103 is proposed to be a potential therapeutical target in inflammatory bowel disease (IBD), as it can form a heterodimeric integrin with ß7 (Etrolizumab, anti-ß7 integrin) on epithelial T cells. Therefore, we aimed to study the frequencies of different intestinal CD103+T-cell subsets, both CD4+ and CD8+, in newly diagnosed, untreated IBD patients at baseline and during follow-up, compared with healthy controls. METHODS: Intestinal biopsies from inflamed segments during colonoscopy and peripheral blood samples were prospectively taken from IBD patients at diagnosis and during follow-up. Blood and single cell suspensions from biopsies were analyzed for CD103+ T-cell subpopulations by flow cytometry and expressed as median percentages of the total T-cell population. RESULTS: In total, 75 Crohn's disease (CD) patients, 49 ulcerative colitis (UC) patients, and 16 healthy controls were included. At presentation, IBD patients displayed lower percentages of CD103+T-cell subsets in inflamed biopsies: 3% (1 to 5) CD103+CD4+ in IBD vs 5% (5 to 7) in healthy controls (P = 0.007) and 9% (4 to 15) CD103+CD8+ compared with 42% (23 to 57) in healthy controls (P = 0.001). The majority of intestinal T cells was composed of CD103-CD4+ T cells (65% [52 to 74]) in IBD compared with 30% (21 to 50) in healthy controls (P = 0.001). In patients with endoscopic remission during follow-up (n = 27), frequencies of CD103+ and CD103-T-cell subsets were comparable with healthy controls. CONCLUSION: At diagnosis, active inflammation in IBD was associated with decreased percentages of both CD103+CD4+ and CD103+CD8+T-cell subsets in colon and ileum biopsies. In active disease during follow-up, these T-cell populations remained low but increased in remission to values comparable with healthy controls. A shift toward more CD103-T cells was observed during active inflammation.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Trato Gastrointestinal/imunologia , Intestinos/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Antígenos CD/metabolismo , Estudos de Casos e Controles , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Feminino , Seguimentos , Humanos , Cadeias alfa de Integrinas/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
18.
Nat Commun ; 10(1): 975, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816112

RESUMO

Innate lymphoid cells (ILC), including natural killer (NK) cells, are implicated in host-defense and tissue-growth. However, the composition and kinetics of NK cells in the intestine during the first year of life, when infants are first broadly exposed to exogenous antigens, are still unclear. Here we show that CD103+ NK cells are the major ILC population in the small intestines of infants. When compared to adult intestinal NK cells, infant intestinal NK cells exhibit a robust effector phenotype, characterized by Eomes, perforin and granzyme B expression, and superior degranulation capacity. Absolute intestinal NK cell numbers decrease gradually during the first year of life, coinciding with an influx of intestinal Eomes+ T cells; by contrast, epithelial NKp44+CD69+ NK cells with less cytotoxic capacity persist in adults. In conclusion, NK cells are abundant in infant intestines, where they can provide effector functions while Eomes+ T cell responses mature.


Assuntos
Intestinos/citologia , Intestinos/imunologia , Células Matadoras Naturais/imunologia , Proteínas com Domínio T/metabolismo , Adulto , Idoso , Antígenos CD/metabolismo , Granzimas/metabolismo , Humanos , Imunidade Inata , Imunofenotipagem , Lactente , Cadeias alfa de Integrinas/metabolismo , Intestinos/crescimento & desenvolvimento , Células Matadoras Naturais/classificação , Células Matadoras Naturais/metabolismo , Pessoa de Meia-Idade , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Perforina/metabolismo , Distribuição Tecidual
19.
Zhonghua Shao Shang Za Zhi ; 35(2): 125-133, 2019 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-30798579

RESUMO

Objective: To observe the effects of basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and vascular endothelial growth factor C (VEGF-C) on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into lymphatic endothelial cells (LECs). Methods: The third to the fifth passage of BMSCs of rats were collected for the following experiments. (1) BMSCs of rats were collected and divided into negative control group, CD90 group, CD44 group, and CD34 group according to the random number table (the same grouping method below), with 3 samples in each group. Phosphate buffer of 5 µL was added to cells in negative control group, and cells in the other 3 groups were added with 5 µL corresponding antibodies respectively. The positive expression of cell surface antigen was detected by flow cytometer. (2) BMSCs of rats in 3 batches were collected and divided into blank control group, VEGF-C group, HGF group, bFGF group, VEGF-C+ HGF group, VEGF-C+ bFGF group, HGF+ bFGF group, and VEGF-C+ HGF+ bFGF group, with 3 samples in each group. Cells in blank control group were added with 2 mL complete medium, cells in VEGF-C group were added with 2 mL complete medium and 10 µL VEGF-C of 10 µg/mL, cells in HGF group were added with 2 mL complete medium and 16 µL HGF of 10 µg/mL, and cells in bFGF group were added with 2 mL complete medium and 20 µL bFGF of 1 µg/mL. Cells in VEGF-C+ HGF group, VEGF-C+ bFGF group, HGF+ bFGF group, and VEGF-C+ HGF+ bFGF group were added with 2 mL complete medium and induction factors with corresponding concentration and volume as above. On 10 d of culture, the morphology of the cells was observed by the inverted phase contrast microscope, and the protein and mRNA expressions of lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE-1), VEGF receptor 3 (VEGFR3), and integrin α9 were detected by Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction respectively. (3) BMSCs of rats were collected and divided into blank control group, HGF+ VEGF-C+ bFGF group, bFGF+ VEGF-C+ HGF group, and VEGF-C+ HGF+ bFGF group, with 3 samples in each group. Cells in blank control group were added with 2 mL complete medium. Cells in HGF+ VEGF-C+ bFGF group were added with 2 mL complete medium, 16 µL HGF of 10 µg/mL, and 10 µL VEGF-C of 10 µg/mL, after 6 hours, 20 µL bFGF of 1 µg/mL was added. Cells in bFGF+ VEGF-C+ HGF group were added with 2 mL complete medium, 20 µL bFGF of 1 µg/mL, and 10 µL VEGF-C of 10 µg/mL, after 6 hours, 16 µL HGF of 10 µg/mL was added. Cells in VEGF-C+ HGF+ bFGF group were simultaneously added with 2 mL complete medium and the same concentration and volume of three inducing factors as above. In addition, BMSCs of rats in another 2 batches were collected and grouped, and they were dealt with the same methods as above except that the interval time of 6 hours in HGF+ VEGF-C+ bFGF group and bFGF+ VEGF-C+ HGF group was adjusted to 12 and 24 hours. On 10 d of culture, protein expressions of LYVE-1, VEGFR3, and integrin α9 were detected by Western blotting. Data were processed with analysis of variance of factorial design, one-way analysis of variance, and least significant difference t test, and Bonferroni correction. Results: (1) The positive expression rates of surface antigen of cells in negative control group, CD90 group, CD44 group, and CD34 group were 0.39%, 99.84%, 99.90%, and 0.57%, respectively. (2) On 10 d of culture, cells in blank control group, HGF group, bFGF group, and HGF+ bFGF group presented long fusiform, while cells in the other groups presented polygonal shape. (3) On 10 d of culture, there were no protein expressions of LYVE-1, VEGFR3, and integrin α9 in cells of blank control group, HGF group, bFGF group, and HGF+ bFGF group. On 10 d of culture, protein expressions of LYVE-1, VEGFR3, and integrin α9 in cells of VEGF-C+ HGF+ bFGF group were significantly higher than those in VEGF-C group (t=24.21, 11.04, 15.43, P<0.01), VEGF-C+ HGF group (t=10.81, 9.93, 10.20, P<0.01), and VEGF-C+ bFGF group (t=11.67, 6.32, 19.00, P<0.01). Protein expressions of LYVE-1 in cells of VEGF-C+ HGF group and VEGF-C+ bFGF group were significantly higher than the protein expression in VEGF-C group (t=8.69, 15.20, P<0.01). Protein expression of VEGFR3 in cells of VEGF-C+ bFGF group was obviously higher than the protein expressions in VEGF-C group and VEGF-C+ HGF group (t=8.67, 7.21, P<0.01). Protein expression of integrin α9 in cells of VEGF-C+ HGF group was obviously higher than the protein expressions in VEGF-C group and VEGF-C+ bFGF group (t=8.80, 8.83, P<0.01). (4) On 10 d of culture, there were no mRNA expressions of LYVE-1, VEGFR3, and integrin α9 in cells of blank control group, HGF group, bFGF group, and HGF+ bFGF group. On 10 d of culture, mRNA expressions of LYVE-1 and VEGFR3 in cells of VEGF-C group were significantly lower than those in VEGF-C+ bFGF group and VEGF-C+ HGF+ bFGF group (t(LYVE-1)=6.22, 18.01, t(VEGFR3)=8.49, 15.34, P<0.01), and mRNA expression of integrin α9 were significantly lower than that in VEGF-C+ HGF group and VEGF-C+ HGF+ bFGF group (t=13.24, 9.65, P<0.01). The mRNA expressions of LYVE-1, VEGFR3, and integrin α9 in cells of VEGF-C+ HGF+ bFGF group were obviously higher than those in VEGF-C+ HGF group and VEGF-C+ bFGF group (t=13.92, 11.95, 13.72, 5.27, 5.64, 9.10, P<0.01). Compared with those of VEGF-C+ bFGF group, the mRNA expression of VEGFR3 of cells in VEGF-C+ HGF group was significantly lower (t=6.91, P<0.01), while the mRNA expression of integrin α9 of cells in VEGF-C+ HGF group was significantly higher (t=11.69, P<0.01). (5) On 10 d of culture at interval time of 6, 12, 24 h, there were no protein expressions of LYVE-1, VEGFR3, or integrin α9 in cells of blank control group. On 10 d of culture at interval time of 6, 12, 24 h, the protein expressions of LYVE-1, VEGFR3, and integrin α9 in cells of HGF+ VEGF-C+ bFGF group, bFGF+ VEGF-C+ HGF group, and VEGF-C+ HGF+ bFGF group were close (F(6 h)=2.25, 2.47, 2.19, F(12 h)=2.93, 1.47, 3.25, F(24 h)=0.28, 0.20, 1.01, P>0.05). Conclusions: VEGF-C is a necessary factor for inducing BMSCs to differentiate into LECs. HGF and bFGF may promote the differentiation by up-regulating the expressions of integrin α9 and VEGFR3 respectively. But the induction effects of the two factors may be independent. The combination of VEGF-C, HGF, and bFGF have the best effects of promoting differentiation.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fator de Crescimento de Hepatócito/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Fator C de Crescimento do Endotélio Vascular/farmacologia , Animais , Células da Medula Óssea/metabolismo , Células Cultivadas , Células Endoteliais , Cadeias alfa de Integrinas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Ratos , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA