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1.
Sheng Wu Gong Cheng Xue Bao ; 35(9): 1571-1580, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31559740

RESUMO

Extracellular matrix (ECM) proteins play an important role in a series of biological processes in the cell, and their abnormal regulation can lead to many diseases. The theoretical ECM reference dataset is the basis for efficient identification of extracellular matrix proteins. Researchers have developed various ECM protein prediction tools based on machine learning methods. In this review, the main strategy of development of ECM protein prediction tools that based on machine learning methods has been introduced. Then, advances and specific characters of the existing ECM protein prediction tools have been summarized. Finally, the challenges and possible improvements of ECM protein prediction tools are discussed.


Assuntos
Matriz Extracelular , Proteínas da Matriz Extracelular
2.
BMC Ophthalmol ; 19(1): 191, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438893

RESUMO

BACKGROUND: To investigate the efficacy and safety of repeated phototherapeutic keratectomies (PTKs) during long-term treatment for corneal dystrophy (CD) in a Chinese pedigree carrying the R124L mutation in TGFBI. METHODS: This was a retrospective review of 20-year medical and genetic records involving five CD patients (10 eyes) from one pedigree. During this period, PTK was conducted for an eye when best-corrected distance visual acuity (BCDVA) reached > 1.0 (LogMAR), due to either primary or recurrent opacities in the cornea. All PTKs were performed by 193-nm excimer laser with or without creation of epithelial flaps. For each eye, routine measurements were conducted for the number of PTKs during follow-up, mean time to recurrence, and BCDVA pre- and post- every PTK (measurements within 3 months from each PTK). Corneal thicknesses measured after the last PTK and at the last visit were analyzed, and subjective satisfaction was assessed. RESULTS: Gene testing revealed an R124L mutation in TGFBI. During 19.60 ± 1.78 years of follow-up, PTKs were conducted twice for three eyes, three times for six eyes, and four times for one eye. After each PTK, effective visual acuity was maintained for 3.60 ± 1.12 years before significant recurrence. BCDVA improved significantly postoperatively than preoperatively for the first PTK for each eye (p < 0.001), as well as the second (p < 0.001) and third one (p < 0.001). After the last PTK and at the final visit, the thinnest corneal thickness was 371.50 ± 56.47 µm and 358.40 ± 101.11 µm, respectively. The average subjective satisfaction score was 8.60 ± 0.89. CONCLUSIONS: Multiple repeated PTKs were effective and safe in a long-term study of CD patients with an R124L mutation in TGFBI.


Assuntos
Córnea/cirurgia , Distrofias Hereditárias da Córnea/cirurgia , Proteínas da Matriz Extracelular/genética , Previsões , Lasers de Excimer/uso terapêutico , Mutação , Ceratectomia Fotorrefrativa/métodos , Fator de Crescimento Transformador beta/genética , Adulto , Idoso , China/epidemiologia , Córnea/patologia , Distrofias Hereditárias da Córnea/epidemiologia , Distrofias Hereditárias da Córnea/genética , DNA/genética , Análise Mutacional de DNA , Proteínas da Matriz Extracelular/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Estudos Retrospectivos , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento , Acuidade Visual
3.
Braz Oral Res ; 33: e058, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31432925

RESUMO

Cementum is the mineralized tissue covering the tooth root that functions in tooth attachment and post-eruptive adjustment of tooth position. It has been reported to be highly similar to bone in several respects but remains poorly understood in terms of development and regeneration. Here, we investigate whether cementocytes, the residing cells in cellular cementum, have the potential to be protagonist in cementum homeostasis, responding to endocrine signals and directing local cementum metabolism. Cells from healthy erupted human teeth were isolated using sequential collagenase/EDTA digestions, and maintained in standard cell culture conditions. A cementocyte-like cell line was cloned (HCY-23, for human cementocyte clone 23), which presented a cementocyte compatible gene expression signature, including the expression of dentin matrix protein 1 ( DMP1 ), sclerostin ( SOST ), and E11/gp38/podoplanin ( E11 ). In contrast, these cells did not express the odontoblast/dentin marker dentin sialoprotein ( DSPP ). HCY-23 cells produced mineral-like nodules in vitro under differentiation conditions, and were highly responsive to inorganic phosphate (Pi). Within the limits of the present study, it can be concluded that cementocytes are phosphate-responsive cells, and have the potential do play a key role in periodontal homeostasis and regeneration.


Assuntos
Técnicas de Cultura de Células/métodos , Cemento Dentário/citologia , Adolescente , Adulto , Análise de Variância , Proteínas Morfogenéticas Ósseas/análise , Proteínas Morfogenéticas Ósseas/genética , Linhagem Celular , Cemento Dentário/metabolismo , Proteínas da Matriz Extracelular/análise , Proteínas da Matriz Extracelular/genética , Feminino , Imunofluorescência , Expressão Gênica , Marcadores Genéticos/genética , Humanos , Masculino , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/genética , Dente Molar/citologia , Fosfatos/farmacologia , Fosfoproteínas/análise , Fosfoproteínas/genética , Sialoglicoproteínas/análise , Sialoglicoproteínas/genética , Fatores de Tempo , Adulto Jovem
4.
Medicine (Baltimore) ; 98(26): e15872, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261495

RESUMO

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer accounts for ∼20% of invasive breast cancers and is associated with poor prognostics. The recent outcome of HER2+ breast cancer treatment has been vastly improved owing to the application of antibody-targeted therapies. Trastuzumab (Herceptin) is a monoclonal antibody designed to target HER2+ breast cancer cells. In addition to improved survival in the adjuvant treatment of HER2+ breast cancer, trastuzumab treatment has also been associated with cardiotoxicity side effect. However, the molecular mechanisms of trastuzumab action and trastuzumab-mediated cardiotoxicity are still not fully understood. Previous research utilized bulk transcriptomics analysis to study the underlining mechanisms, which relied on averaging molecular signals from bulk tumor samples and might have overlooked key expression features within breast cancer tumor. In contrast to previous research, we compared the single cancer cell level transcriptome profile between trastuzumab-treated and nontreated patients to reveal a more in-depth transcriptome profile. A total of 461 significantly differential expressed genes were identified, including previously defined and novel gene expression signatures. In addition, we found that trastuzumab-enhanced MGP gene expression could be used as prognostics marker for longer patient survival in breast invasive carcinoma patients, and validated our finding using TCGA (The Cancer Genome Atlas) breast cancer dataset. Moreover, our study revealed a 48-gene expression signature that is associated with cell death of cardiomyocytes, which could be used as early biomarkers for trastuzumab-mediated cardiotoxicity. This work is the first study to look at single cell level transcriptome profile of trastuzumab-treated patients, providing a new understanding of the molecular mechanism(s) of trastuzumab action and trastuzumab-induced cardiotoxicity side effects.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Transcriptoma/efeitos dos fármacos , Trastuzumab/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Projetos Piloto , Prognóstico , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Análise de Célula Única , Análise de Sobrevida
5.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(3): 248-252, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31218856

RESUMO

OBJECTIVE: To verify the effect of the mutant gene vps4b on the expression of tooth development-related proteins, dentin sialophosphoprotein (DSPP) and collagenⅠ (COL-Ⅰ). METHODS: Paraffin tissue sections of the first molar tooth germ were obtained from the heads of fetal mice at the embryonic stages of 13.5, 14.5, and 16.5 days and from the mandibles of larvae aged 2.5 and 7 days after birth. The immunohistochemical method was used to detect the expression and location of DSPP and COL-Ⅰ in wild-type mouse and vps4b knockout mouse. RESULTS: DSPP and COL-Ⅰ were not found in the bud and cap stages of wild-type mouse molar germ. In the bell stage, DSPP was positively expressed in the inner enamel epithelium and dental papilla, whereas COL-Ⅰ was strongly expressed in the dental papilla and dental follicle. During the secretory and mineralized periods, DSPP and COL-Ⅰ were intensely observed in ameloblasts, odontoblasts, and dental follicles, but COL-Ⅰ was also expressed in the dental papilla. After vps4b gene knockout, DSPP was not expressed in the dental papilla of the bell stage and in the dental papilla and dental follicle of the secretory phase. The expression position of COL-Ⅰ in the bell and mineralization phase was consistent with that in the wild-type mice. Moreover, the expression of COL-Ⅰ in the dental papilla changed in the secretory stage. CONCLUSIONS: Gene vps4b plays a significant role in the development of tooth germ. The expression of DSPP and COL-Ⅰ may be controlled by gene vps4b and regulates the development of tooth dentin and cementum together with vps4b.


Assuntos
ATPases Associadas a Diversas Atividades Celulares , Complexos Endossomais de Distribuição Requeridos para Transporte , Proteínas da Matriz Extracelular , Fosfoproteínas , Sialoglicoproteínas , ATPases Associadas a Diversas Atividades Celulares/genética , Animais , Colágeno/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Proteínas da Matriz Extracelular/metabolismo , Camundongos , Camundongos Knockout , Dente Molar , Odontoblastos , Fosfoproteínas/metabolismo , Sialoglicoproteínas/metabolismo , Germe de Dente
6.
APMIS ; 127(8): 588-593, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31233243

RESUMO

Microfibrillar-associated protein 4 (MFAP4) is a non-structural matrix protein with cell regulatory activities and a potential as seromarker for fibrosis. We aimed to study the occurrence of MFAP4 in the synovial membrane from patients with rheumatoid arthritis (RA) vs osteoarthritis (OA). Formaldehyde-fixed synovial tissue sections, from patients with RA (N = 6) and OA (N = 6) undergoing total hip arthroplasty, were deparaffinized and immunostained with monoclonal antibodies against MFAP4. Elastin was detected using ElastiKit. MFAP4 in serum (sMFAP4) and synovial fluid was measured by an immunoassay. MFAP4 was present in synovial biopsies from both RA and OA patients, particularly prominent in deep arterioles where it colocalized with elastin. Notably however, MFAP4 was absent from the internal elastic lamina in RA arterioles irrespective of disease duration and synovitis activity, while present although with irregular staining patterns in OA specimens. sMFAP4 was increased in RA and OA serum vs healthy controls: median (interquartile range) 29.8 (25.3-39.1) and 25.5 U/L (18.1-43.3) vs 17.7 U/L (13.7-21.2), p = 0.006 and p = 0.02, respectively The concentration of synovial fluid was lower than in serum in both RA and OA. These findings may suggest that MFAP4 is involved in adaptive vessel wall remodeling associated with chronic joint disease.


Assuntos
Artrite Reumatoide/imunologia , Proteínas de Transporte/análise , Proteínas da Matriz Extracelular/análise , Glicoproteínas/análise , Osteoartrite/imunologia , Membrana Sinovial/imunologia , Idoso , Anticorpos Monoclonais/imunologia , Biomarcadores/análise , Proteínas de Transporte/imunologia , Estudos de Casos e Controles , Proteínas da Matriz Extracelular/imunologia , Feminino , Glicoproteínas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Líquido Sinovial/química , Membrana Sinovial/patologia
7.
Zhonghua Yi Xue Za Zhi ; 99(20): 1553-1557, 2019 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-31154721

RESUMO

Objective: To investigate the expression and prognosis effect of methylation-regulated SLIT3 and SPRCL1 genes in smoking-related lung adenocarcinoma. Methods: The expression levels of SLIT3 and SPARCL1 in cigarette smoke-induced malignant transformed cell (S30) and lung adenocarcinoma (LUAD) cell lines were measured by real-time fluorescence quantitative PCR (qPCR). Datasets of mRNA expression, DNA methylation and patient information data were obtained from The Cancer Genome Altas (TCGA) database. The mRNA expression levels of SLIT3 and SPARCL1 were validated in LUAD tissues. The 10-year survival curve of LUAD patients with different smoking history was plotted, and the correlation between mRNA expression level and DNA methylation level of LUAD patients was further analyzed. S30 cells were treated with 5-azacytidine (5-aza), an inhibitor of DNA methyltransferase, to analyze the methylation regulatory mechanism of SLIT3 and SPRCL1. Results: The qPCR results showed the significant down-regulation of SLIT3 and SPARCL1 in S30 cell and four LUAD cell lines (SLIT3: 0.493±0.134 and 0.041±0.014, 0.161±0.023, 0.277±0.055, 0.035±0.005; SPARCL1: 0.507±0.131 and 0.453±0.045, 0.420±0.040, 0.153±0.035, 0.430±0.050; all P<0.01). Bioinformatics analysis showed that SLIT3 and SPARCL1 were low expressed in LUAD tissue (8.12±1.58 vs 10.84±0.69 and 11.46±1.06 vs 13.57±0.67; both P<0.001) compared with adjacent peritumoral tissues, and expression levels of SLIT3 and SPARCL1 were significantly correlated with smoking history (both P<0.001). Non-smoker with high expression of SLIT3 and SPARCL1 was associated with better prognosis among LUAD patients. There was a significant negative correlation between promoter methylation and mRNA expression level of the two genes (r=-0.208, -0.574; both P<0.001). 5-aza treatment significantly up-regulated the expression levels of SLIT3 and SPARCL1 genes in S30 cells (2.137±0.281, 3.657±0.882; both P<0.01). Conclusion: SLIT3 and SPARCL1 can be regulated by DNA methylation and down-regulated in LUAD tissue, which has important prognostic significance on the smoking-induced LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas de Ligação ao Cálcio , Proteínas da Matriz Extracelular , Humanos , Proteínas de Membrana , Prognóstico , Fumar
8.
Cell Physiol Biochem ; 53(1): 87-100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31204440

RESUMO

BACKGROUND/AIMS: Different components of the tumor microenvironment can be either tumor-promoting or tumor-suppressive agents depending on factors which are not fully understood. Fibulins are components of the extracellular matrix from different tissues and constitute a clear example of this dual function. In fact, fibulins may either support tumor growth or abolish progression of malignant cells depending on the crosstalk between tumor cells and their surrounding stroma through mechanisms that remain to be elucidated. Among all fibulins, fibulin-5 contains a particular structural hallmark which consists in the presence of a RGD motif within its architecture. Previous reports have highlighted the importance of the interaction of this motif with integrins, and not only in normal functions but also in a tumor context. METHODS: Site-Directed Mutagenesis technique was employed to introduce the change RGD to RGE (RGD-to-RGE) within Fbln5 cDNA sequence. Cell proliferation was measured using the MTT assay or by counting Ki-67 positive cell nuclei. Cell adhesion was analysed using culture plates coated with different extracellular matrix components. Cell invasion was evaluated using 24-well Matrigel-coated invasion chambers, and mammosphere formation was monitored using ultralow attachment culture plates. BALB/c mice were employed to induce subcutaneous tumors. RESULTS: The RGD-to-RGE change alters the capacity of breast cancer cells to adhere to different extracellular matrix proteins as well as to αvß3 and α5ß1 integrins, and promotes protumor effects using different cell-based assays. Moreover, 4T1 cells, a mouse breast cancer cell line model, shows an increased capacity to generate tumors when exogenously expresses fibulin-5 with a RGD-to-RGE change, and such capacity is similar to that shown for 4T1 cells with an interfered Fbln5 gene. CONCLUSION: These data highlight the importance of the RGD motif of fibulin-5 to induce antitumor effects and provide new insights into the involvement of fibulins in tumor processes.


Assuntos
Adesão Celular/efeitos dos fármacos , Proteínas da Matriz Extracelular/farmacologia , Oligopeptídeos/metabolismo , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Proteínas da Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/uso terapêutico , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mutagênese Sítio-Dirigida , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oligopeptídeos/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Transplante Homólogo , Vimentina/metabolismo
9.
Nat Immunol ; 20(7): 915-927, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31110316

RESUMO

The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy.


Assuntos
Perfilação da Expressão Gênica , Interferon Tipo I/metabolismo , Queratinócitos/metabolismo , Túbulos Renais/citologia , Túbulos Renais/metabolismo , Nefrite Lúpica/genética , Nefrite Lúpica/metabolismo , Transcriptoma , Biópsia , Linhagem da Célula/genética , Biologia Computacional/métodos , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Fibrose , Perfilação da Expressão Gênica/métodos , Humanos , Nefrite Lúpica/patologia , Ligação Proteica , Transdução de Sinais , Análise de Célula Única , Pele/imunologia , Pele/metabolismo , Pele/patologia
10.
Adv Exp Med Biol ; 1132: 23-32, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037621

RESUMO

Periostin is a secretory matricellular protein with a multi-domain structure that is composed of an amino-terminal EMI domain, a tandem repeat of four FAS 1 domains, and a carboxyl-terminal domain (CTD). Periostin has been suggested to function as a scaffold for assembly of several extracellular matrix proteins as well as its accessory proteins (Fig. 3.1, Table 3.1), which underlies highly sophisticated extracellular architectures. This scaffold function is likely due to periostin's multi-domain structure, in which the adjacent domains in periostin interact with different kinds of proteins, put these interacting proteins in close proximity, and promote intermolecular interactions between these proteins, leading to their assembly into a large complex. In this chapter, I introduce the proteins that interact with each of the adjacent domains in periostin, and discuss how the multi-domain structure of periostin functions as a scaffold for the assembly of the interacting proteins, and how it underlies construction of highly sophisticated extracellular architectures.


Assuntos
Moléculas de Adesão Celular/química , Proteínas da Matriz Extracelular/química , Humanos , Domínios Proteicos
11.
Adv Exp Med Biol ; 1132: 35-41, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037622

RESUMO

Cardiac muscle (the myocardium) is a unique arrangement of atria and ventricles that are spatially and electrically separated by a fibrous border. The spirally-arranged myocytes in both left and right ventricles are tethered by the component molecules of the cardiac extracellular matrix (ECM), including fibrillar collagen types I and III. Loss of normal arrangement of the ECM with either too little (as is observed in acute myocardial infarction) or too much (cardiac fibrosis in chronic post-myocardial infarction) is the primary contributor to cardiac dysfunction and heart failure. Matricellular proteins exist as non-structural signaling moieties in the ECM, and in the context of cardiac hypertrophy and heart failure, secreted 90 kDa periostin protein has attracted intense scrutiny during the past decade. Secreted periostin is now recognized for its important role in ECM development and maturation, as well as cellular adhesion. The novel mechanisms of periostin function include its role as a mediator of cell-to-matrix signaling, cell survival, and epithelial-mesenchymal transition (EMT). A number of recent studies have examined the hypothesis that periostin is a major contributor to ECM remodeling in the heart, and a number of very recent studies underscore its important role. This review examines recent developments in the mechanisms of periostin function in the normal heart and vasculature, and discusses recent advances which underpin its putative role in the development of cardiovascular disease. Periostin expression is very low at baseline in healthy tissues, but is re-expressed in damaged heart and in vessel walls after injury, in activated cardiac myofibroblasts and vascular smooth muscle cells, respectively. For this reason, periostin may be exploited for investigation of mechanisms of cardiac fibrosis , and we speculate that data generated from studies utilizing this approach may shed light on the timing for application of periostin-specific therapies to quell cardiac fibrosis and associated cardiac dysfunction.


Assuntos
Moléculas de Adesão Celular/fisiologia , Infarto do Miocárdio , Miofibroblastos/citologia , Remodelação Ventricular , Proteínas da Matriz Extracelular , Ventrículos do Coração , Humanos , Miocárdio , Fenótipo
12.
Adv Exp Med Biol ; 1132: 73-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037626

RESUMO

Periostin is a secreted matricellular protein that primarily interacts with type I collagen and fibronectin extracellular matrix proteins, and is widely distributed in tissues rich in collagen-rich connective tissues, including the periodontal ligament. Its expression in these tissues is especially regulated by mechanical load. While the expression and regulation of periostin in the teeth of murine models and cell lines is well known, its presence in human teeth is poorly documented. Here we update and summarize the available data on the distribution of periostin in the human periodontal ligament, gingiva and dental pulp.


Assuntos
Moléculas de Adesão Celular/fisiologia , Polpa Dentária/fisiologia , Gengiva/fisiologia , Ligamento Periodontal/fisiologia , Dente , Animais , Proteínas da Matriz Extracelular , Humanos , Camundongos
13.
Cell Physiol Biochem ; 52(6): 1553-1568, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31135123

RESUMO

BACKGROUND/AIMS: Despite, several studies demonstrating pro-metastatic effects of the metalloproteinase ADAMTS1 in breast cancer, its role in facilitating the metastatic cascade remains unclear. To date there have been limited studies that have examined the expression of ADAMTS1 in primary and metastatic breast cancer tissues. METHODS: We assessed ADAMTS1 mRNA levels in publically available breast cancer sets and analysed ADAMTS1 protein levels by immunohistochemistry in breast tissue microarrays containing normal breast tissue (n=9), primary invasive ductal breast carcinomas (n=79) and metastatic lesions (n=58). To understand the underlying events influenced by ADAMTS1 and provide a mechanism by which tumors expressing this protease promote metastasis, we assessed the ability of PyMT/Adamts1+/+, PyMT/Adamts1+/- and PyMT/Adamts1-/- primary mammary cancer cells to adhere to matrigel and migrate or invade towards a chemoattractive environment. RESULTS: High ADAMTS1 expression was associated with reduced disease-free survival, distant metastasis free-survival and overall survival in breast cancer patients with node negative disease. Although ADAMTS1 expression was reduced in primary breast cancers compared to normal tissue and not elevated in metastatic lesions, high ADAMTS1 immunostaining was associated with a higher number of positive lymph nodes (p=0.006) and the presence of distant metastasis (p=0.023). Depletion of Adamts1 in mammary cancer cells impeded their adhesion to a biological matrix substratum and diminished cell migration but not invasion. CONCLUSION: The effects observed on cell adhesion and migration demonstrates a potential mechanism whereby ADAMTS1 promotes breast cancer metastasis.


Assuntos
Proteína ADAMTS1/metabolismo , Neoplasias da Mama/patologia , Proteínas da Matriz Extracelular/metabolismo , Proteína ADAMTS1/genética , Animais , Neoplasias da Mama/mortalidade , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Camundongos , Camundongos Transgênicos , Estadiamento de Neoplasias , Prognóstico
14.
Cell Host Microbe ; 25(4): 475-476, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974079

RESUMO

Since the inner ear is an important but sensitive organ of hearing, bacteria-driven immune responses must be tightly controlled. In this issue of Cell Host & Microbe, Jung et al. (2019) demonstrate that cleaved cochlin plays a dual role to trap bacteria and recruit immune cells to improve ear function.


Assuntos
Orelha Interna , Pseudomonas aeruginosa , Proteínas da Matriz Extracelular , Imunidade Inata
15.
J Mol Histol ; 50(3): 285-294, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30993430

RESUMO

The aim of this study was to ascertain whether, like many cell types in cartilaginous tissues if type XI collagen was a pericellular component of annulus fibrosus (AF) cells and chondrocytes. Fine fibrillar networks were visualised which were perlecan, HS (MAb 10E4) and type XI collagen positive. Heparitinase-III pre-digestion abolished the type XI collagen and 10E4 localisation in these fibrillar assemblies demonstrating a putative HS mediated interaction which localised the type XI collagen. Type XI collagen was confirmed to be present in the Heparitinase III treated AF monolayer media samples by immunoblotting. Heparitinase-III generated ΔHS stub epitopes throughout these fibrillar networks strongly visualised by MAb 3-G-10. Monolayers of murine hip articular chondrocytes from C57BL/6 and Hspg2 exon 3 null mice also displayed pericellular perlecan localisations, however type XI collagen was only evident in the Wild type mice. Perlecan was also immunolocalised in control and murine knee articular cartilage from the two mouse genotypes subjected to a medial meniscal destabilisation procedure which induces OA. This resulted in a severe depletion of perlecan levels particularly in the perlecan exon 3 null mice and was consistent with OA representing a disease of the pericellular matrix. A model was prepared to explain these observations between the NPP type XI collagen domain and HS chains of perlecan domain-I in the pericellular matrix of AF cells which likely contributed to cellular communication, tissue stabilization and the regulation of extracellular matrix homeostasis.


Assuntos
Anel Fibroso/efeitos dos fármacos , Colágeno Tipo XI/genética , Proteoglicanas de Heparan Sulfato/genética , Animais , Anel Fibroso/metabolismo , Anel Fibroso/patologia , Cartilagem Articular/crescimento & desenvolvimento , Cartilagem Articular/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Éxons/genética , Matriz Extracelular/genética , Proteínas da Matriz Extracelular/genética , Homeostase/genética , Disco Intervertebral/crescimento & desenvolvimento , Disco Intervertebral/metabolismo , Camundongos , Polissacarídeo-Liase/farmacologia
16.
J Mol Histol ; 50(3): 253-261, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30937700

RESUMO

Nel-like molecule-1 (NELL-1) is a novel highly specific growth factor that can induce osteoblast differentiation and bone formation as well as odontoblast differentiation. Recent studies have suggested that NELL-1 can synergistically increase bone formation and regeneration with bone morphogenetic protein 2 (BMP2) and inhibit adverse effects induced by BMP2. This study aimed to evaluate the combined effects of NELL-1 and BMP2 on rat pulp repair. The experiment used healthy non-carious maxillary first molars from 60 Wistar rats. Exposed pulps were capped with NELL-1 plus BMP2, NELL-1 alone, and BMP2 alone, and each was absorbed onto a sterile collagen sponge. In the control samples, the collagen sponge alone and Dycal were used as capping agents. After l, 2 and 4 weeks, the rats were sacrificed. The formation of reparative dentin, as well the situation of pulp repair, was detected by hematoxylin-eosin (HE) staining; moreover, the expression of dentin specific protein-dentin sialophosphoprotein (DSPP) and the pro-inflammatory cytokines interleukin-6 (IL6) and interleukin-8 (IL8) was detected by immunohistochemical staining. Quantitative real-time PCR experiment was used to investigate the mRNA levels of IL6 and IL8. The results showed that pulp capping with NELL-1 plus BMP2 in rats had superior ability in inducing reparative dentin formation with dentin tubules and in reducing the inflammatory cell response compared with the other groups. These findings suggested that combined use of NELL-1 and BMP2 could positively regulate pulp repair.


Assuntos
Proteína Morfogenética Óssea 2/genética , Capeamento da Polpa Dentária , Polpa Dentária/crescimento & desenvolvimento , Proteínas do Tecido Nervoso/genética , Animais , Proteína Morfogenética Óssea 2/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Polpa Dentária/metabolismo , Dentina/metabolismo , Proteínas da Matriz Extracelular/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Interleucina-6/genética , Interleucina-8/genética , Proteínas do Tecido Nervoso/administração & dosagem , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Fosfoproteínas/genética , Ratos , Ratos Wistar , Sialoglicoproteínas/genética
17.
Int J Mol Sci ; 20(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987093

RESUMO

Advanced upper urinary tract urothelial carcinoma (UTUC) is often associated with poor oncologic outcomes. The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) protein, belongs to the SPARC-related family of matricellular proteins. Much literature has been published describing the role of SPARCL1 in the prognosis many cancers. In this study, methylated promoter regions in high-grade and high-stage upper urinary urothelial tumours compared with normal urothelium were analyzed and revealed that SPARCL1 was the most significantly hypermethylated gene in UTUC tissues. Then we prospectively collected UTUC samples and adjacent normal urothelium for pyrosequencing validation, identifying significant CpG site methylation in UTUC tissues. In addition, SPARCL1 RNA levels were significantly lower in UTUC samples. Multivariate Cox regression analysis from 78 patients with solitary renal pelvic or ureteral pT3N0M0 urothelial carcinomas revealed that only negative SPARCL1 expression and nonpapillary tumour architecture were independently associated with systemic recurrence (p = 0.011 and 0.008, respectively). In vitro studies revealed that the behaviour of BFTC-909 cells was less aggressive and more sensitive to radiation or chemotherapy after SPARCL1 overexpression. Thus, SPARCL1 could be considered as a prognostic marker and help decision-making in clinical practice.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Metilação de DNA/genética , Proteínas da Matriz Extracelular/genética , Neoplasias Urológicas/genética , Neoplasias Urológicas/patologia , Urotélio/patologia , Idoso , Sequência de Bases , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Estudos de Coortes , Metilação de DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Humanos , Masculino , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Regiões Promotoras Genéticas/genética , Análise de Regressão , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/radioterapia
18.
PLoS Genet ; 15(4): e1007739, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30990817

RESUMO

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.


Assuntos
Hexoquinase/genética , Subunidade alfa de Receptor de Interleucina-18/genética , Oxiemoglobinas/metabolismo , Sono/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Moléculas de Adesão Celular Neuronais/genética , Biologia Computacional , Proteínas da Matriz Extracelular/genética , Feminino , Redes Reguladoras de Genes , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Hipóxia/sangue , Hipóxia/genética , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas do Tecido Nervoso/genética , Oxigênio/sangue , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Serina Endopeptidases/genética , Síndromes da Apneia do Sono/sangue , Síndromes da Apneia do Sono/genética , Adulto Jovem
19.
Int J Mol Sci ; 20(7)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970594

RESUMO

The cell microenvironment plays a pivotal role in mediating cell adhesion, survival, and proliferation in physiological and pathological states. The relevance of extracellular matrix (ECM) proteins in cell fate control is an important issue to take into consideration for both tissue engineering and cell biology studies. The glycosylation of ECM proteins remains, however, largely unexplored. In order to investigate the physio-pathological effects of differential ECM glycosylation, the design of affordable chemoselective methods for ECM components glycosylation is desirable. We will describe a new chemoselective glycosylation approach exploitable in aqueous media and on non-protected substrates, allowing rapid access to glyco-functionalized biomaterials.


Assuntos
Materiais Biocompatíveis/metabolismo , Técnicas de Cultura de Células/métodos , Proteínas da Matriz Extracelular/metabolismo , Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Colágeno/química , Colágeno/farmacologia , Glicosilação , Humanos
20.
Molecules ; 24(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003546

RESUMO

ανß3 and α5ß1 are essential glycoproteins involved in the pathogenesis of rheumatoid arthritis (RA). Understanding of the role these integrins play in disease have been analyzed via description of cells-expressing ανß3 and α5ß1 and their mediators to trigger inflammation. ανß3 and α5ß1 facilitate cells-ECM and cell-cell communication, producing pro-inflammatory factors. Pro-inflammatory factors are essential for the building of undesirable new blood vessels termed angiogenesis which can further lead to destruction of bones and joints. Despite many attempts to target these glycoproteins, there are still some problems, therefore, there is still interest in understanding the synergistic role these integrins play in the pathogenesis of RA. The purpose of this review is to gain insights into the biological effects of ανß3 and α5ß1 in synovial tissues that are relevant to pathogenesis and therapy of RA.


Assuntos
Artrite Reumatoide/metabolismo , Integrina alfa5beta1/metabolismo , Integrina alfaVbeta3/metabolismo , Artrite Reumatoide/patologia , Artrite Reumatoide/terapia , Comunicação Celular , Proteínas da Matriz Extracelular/metabolismo , Humanos , Terapia de Alvo Molecular
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