Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.282
Filtrar
1.
Nat Commun ; 12(1): 2118, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837181

RESUMO

Hematopoietic stem cells (HSCs) in adult bone marrow (BM) are usually maintained in a state of quiescence. The cellular mechanism coordinating the balance between HSC quiescence and differentiation is not fully understood. Here, we report that galactose-binding lectin-3 (galectin-3; Gal-3) is upregulated by Tie2 or Mpl activation to maintain quiescence. Conditional overexpression of Gal-3 in mouse HSCs under the transcriptional control of Tie2 or Vav1 promoters (Gal-3 Tg) causes cell cycle retardation via induction of p21. Conversely, the cell cycle of long-term repopulating HSCs (LT-HSCs) in Gal-3-deficient (Gal-3-/-) mice is accelerated, resulting in their exhaustion. Mechanistically, Gal-3 regulates p21 transcription by forming a complex with Sp1, thus blocking cell cycle entry. These results demonstrate that Gal-3 is a negative regulator of cell-cycling in HSCs and plays a crucial role in adult hematopoiesis to prevent HSC exhaustion.


Assuntos
Células-Tronco Adultas/fisiologia , Ciclo Celular/fisiologia , Galectina 3/metabolismo , Hematopoese/genética , Células-Tronco Hematopoéticas/fisiologia , Animais , Diferenciação Celular/genética , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21/genética , Feminino , Galectina 3/genética , Camundongos , Camundongos Knockout , Modelos Animais , Receptor TIE-2/metabolismo , Receptores de Trombopoetina/metabolismo , Fator de Transcrição Sp1/metabolismo , Ativação Transcricional , Regulação para Cima
2.
Life Sci ; 274: 119347, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33716065

RESUMO

Pulmonary vascular remodelling is one of the most important factors for pulmonary hypertension (PH). Galectin-3 (Gal-3) is a ß-galactoside-binding lectin. In the latest literature, Gal-3 has been reported to be involved in pulmonary vascular remodelling, and its underlying mechanism is unclear. Our research aims to prove the effect of Gal-3 on the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMC) induced by transforming growth factor ß1 (TGF-ß1) and to study its mechanism. In vivo experiment: In Sprague-Dawley (SD) rats, monocrotaline was injected intraperitoneally to establish a PH model, and the Gal-3 inhibitor (modified citrus pectin, MCP) 28 Ds was administered in the stomach. The results indicate that Gal-3 and TGF-ß1 may be involved in the occurrence and development of PH, which may be related to the Smad2/3 signalling pathway. In vitro experiment: Human pulmonary artery smooth muscle cells were pretreated with the Gal-3 inhibitor (MCP) for 24 h, then TGF-ß1 or Gal-3 was administered to the cells for 24 h. The results show that exogenous TGF-ß1 and Gal-3 can activate the downstream Smad2/3 signalling pathway, and increase the proliferation and migration ability of HPASMC. However, the Gal-3 inhibitor (MCP) inhibited these effects. Further results display that TGF-ß1 and Gal-3 could mutually regulate the protein and mRNA expression levels. In summary, the results of this study indicate that Gal-3 regulates the Smad2/3 signalling pathway through protein interaction with TGF-ß1, in turn regulates the proliferation and migration of HPASMC, thereby regulating the occurrence and development of PH.


Assuntos
Movimento Celular , Proliferação de Células , Galectina 3/metabolismo , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Células Cultivadas , Galectina 3/genética , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética
4.
J Vis Exp ; (166)2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33369604

RESUMO

Classic depletion-reconstitution experiments indicate that galectin-3 is a required splicing factor in nuclear extracts. The mechanism of incorporation of galectin-3 into the splicing pathway is addressed in this paper. Sedimentation of HeLa cell nuclear extracts on 12%-32% glycerol gradients yields fractions enriched in an endogenous ~10S particle that contains galectin-3 and U1 snRNP. We now describe a protocol to deplete nuclear extracts of U1 snRNP with concomitant loss of splicing activity. Splicing activity in the U1-depleted extract can be reconstituted by the galectin-3 - U1 snRNP particle trapped on agarose beads covalently coupled with anti-galectin-3 antibodies. The results indicate that the galectin-3 - U1 snRNP - pre-mRNA ternary complex is a functional E complex leading to intermediates and products of the splicing reaction and that galectin-3 enters the splicing pathway through its association with U1 snRNP. The scheme of using complexes affinity- or immuno-selected on beads to reconstitute splicing activity in extracts depleted of a specific splicing factor may be generally applicable to other systems.


Assuntos
Galectina 3/genética , Microesferas , Splicing de RNA/genética , Ribonucleoproteína Nuclear Pequena U1/metabolismo , Núcleo Celular/metabolismo , Galectina 3/metabolismo , Células HeLa , Humanos , Peptídeos/metabolismo , Precursores de RNA/metabolismo , Ribonucleoproteína Nuclear Pequena U1/genética
5.
PLoS One ; 15(12): e0238540, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33347507

RESUMO

BACKGROUND: Autoimmune hepatitis (AIH) is a disorder of unknown etiology in which immune-mediated liver injury progress to cirrhosis or hepatocellular carcinoma (HCC). The aim of the present study was to determine whether circulating soluble TIM3 (sTIM3) is elevated in patients with AIH patients and whether sTIM-3 levels are associated with clinical parameters of AIH. METHODS: We enrolled 123 Japanese patients with AIH who were identified from the National Hospital Organization-AIH-liver-network database, as well as 32 patients with chronic hepatitis C (CHC), 30 patients with primary biliary cholangitis (PBC) and healthy control subjects. Serum sTIM-3 concentrations were quantified by ELISA. RESULTS: Serum levels of sTIM-3 were significantly higher in AIH patients (median 4865 pg/ml; [interquartile range (IQR); 3122-7471]) compared to those in CHC (1026 pg/ml [IQR: 806-1283] p<0.001), PBC (2395 pg/ml [IQR: 2012-3422] p<0.001) or healthy controls (1285 pg/ml [IQR: 1098-1812] p<0.001). In AIH group, serum sTIM-3 were correlated with alanine aminotransferase (ALT), or total bilirubin (TB) and negatively correlated with serum levels of albumin (Alb). Serum levels of sTIM-3 were also strongly correlated with Mac-2 binding protein glycosylation isomer (M2BPGi) levels, but did not correlate with the histological grade of liver fibrosis. Steroid treatment of AIH patients significantly reduced serum sTIM-3 levels (2147±623pg/ml versus 1321±378pg/ml, p<0.001). CONCLUSIONS: Circulating sTIM-3 levels were elevated in AIH patients and are associated with AIH disease activity and AIH-related liver damage. These findings indicate that serum sTIM-3 correlated with disease status of AIH and could be useful biomarkers to detect autoimmune-mediated liver injury. Our data suggest a possible link between the TIM-3/GAL-9 pathway and AIH severity or phenotype, and further investigations of the TIM-3 pathway and AIH pathophysiology is warranted.


Assuntos
Galectina 3/metabolismo , Hepatite Autoimune/imunologia , Hepatite Autoimune/metabolismo , Domínios de Imunoglobulina/imunologia , Fígado/imunologia , Mucina-3/metabolismo , Linfócitos T/imunologia , Idoso , Alanina Transaminase/imunologia , Albuminas/metabolismo , Bilirrubina/metabolismo , Feminino , Glicosilação , Hepatite C Crônica/imunologia , Hepatite C Crônica/metabolismo , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Linfócitos T/metabolismo
6.
Exp Biol Med (Maywood) ; 245(16): 1425-1427, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32838557

RESUMO

IMPACT STATEMENT: There could be a close relationship between periodontal diseases (PDs) severity and Covid-19 infections. This relationship could be caused by Galectin-3-mediated increased immune response and increased viral attachment. Keeping PDs under control and maintaining rigorous oral hygiene during this troubled Covid-19 pandemic period is very important.Patients with older age and pre-existing conditions like cardiovascular disease, hypertension, diabetes, and obesity are in the higher risk group for developing severe Covid-19 infections. The inflammatory pathways that are involved in these conditions are the same pathways that we see in periodontal diseases (PDs). This raises a significant question: Is PD a pre-existing condition that can increase the risk of developing severe Covid-19 infection? Several studies have shown that Galectins play a key role in the homeostasis of immune cells, and recently, a relationship was found between Covid-19 and Galectin-3 (Gal-3).It has been determined that an important area in the spike protein of Coronavirus-19 is almost exactly the same as the morphology of Gal-3, and these spike proteins are critical for the entry of the virus into host cells. We suspect that there is enough evidence to support a close relationship between PDs severity and Covid-19 infections. There is accumulating evidence to suggest a relationship between the severity of PD and the risk of infection with Covid-19, which requires further investigation. This relationship could be caused by Gal-3-mediated increased immune response and increased viral attachment. In this context, we want to emphasize the importance of keeping PD under control by maintaining rigorous oral hygiene during this troubled Covid-19 pandemic period. We would also like to point out the possibility that having PD may be a pre-disposition toward developing a severe Covid-19 infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/etiologia , Galectina 3/metabolismo , Doenças Periodontais/complicações , Pneumonia Viral/etiologia , Betacoronavirus/patogenicidade , Galectina 3/sangue , Galectina 3/imunologia , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Doenças Periodontais/etiologia , Doenças Periodontais/virologia , Fatores de Risco
7.
Am J Pathol ; 190(9): 1789-1800, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32473918

RESUMO

We studied the role of galectin-3 (Gal-3) in the expression of alternative activation markers (M2) on macrophage, cytokines, and fibrosis through the temporal evolution of healing, ventricular remodeling, and function after myocardial infarction (MI). C57BL/6J and Gal-3 knockout mice (Lgals3-/-) were subjected to permanent coronary ligation or sham. We studied i) mortality, ii) macrophage infiltration and expression of markers of alternative activation, iii) cytokine, iv) matrix metalloproteinase-2 activity, v) fibrosis, and vi) cardiac function and remodeling. At 1 week post-MI, lack of Gal-3 markedly attenuated F4/80+ macrophage infiltration and significantly increased the expression of Mrc1 and Chil1, markers of M2 macrophages at the MI zone. Levels of IL-10, IL-6, and matrix metalloproteinase-2 were significantly increased, whereas tumor necrosis factor-α, transforming growth factor-ß, and fibrosis were remarkably attenuated at the infarct zone. In Gal-3 knockout mice, scar thinning ratio, expansion, and cardiac remodeling and function were severely affected from the onset of MI. At 4 weeks post-MI, the natural evolution of fibrosis in Gal-3 knockout mice was also affected. Our results suggest that Gal-3 is essential for wound healing because it regulates the dynamics of macrophage infiltration, proinflammatory and anti-inflammatory cytokine expression, and fibrosis along the temporal evolution of MI in mice. The deficit of Gal-3 affected the dynamics of wound healing, thus aggravating the evolution of remodeling and function.


Assuntos
Galectina 3/metabolismo , Macrófagos/patologia , Infarto do Miocárdio/patologia , Remodelação Ventricular/fisiologia , Cicatrização/fisiologia , Animais , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/metabolismo
8.
Chemistry ; 26(43): 9620-9631, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32368810

RESUMO

The synthesis of tailored bioactive carbohydrates usually comprises challenging (de)protection steps, which lowers synthetic yields and increases time demands. We present here a regioselective single-step introduction of benzylic substituents at 3-hydroxy groups of ß-d-galactopyranosyl-(1→1)-thio-ß-d-galactopyranoside (TDG) employing dibutyltin oxide in good yields. These glycomimetics act as inhibitors of galectins-human lectins, which are biomedically attractive targets for therapeutic inhibition in, for example, cancerogenesis. The affinity of the prepared glycomimetics to galectin-1 and galectin-3 was studied in enzyme-linked immunosorbent (ELISA)-type assays and their potential to inhibit galectin binding on the cell surface was shown. We used our original in vivo biotinylated galectin constructs for easy detection by flow cytometry. The results of the biological experiments were compared with data from molecular modeling with both galectins. The present work reveals a facile and elegant synthetic route for the preparation of TDG-derived glycomimetics that exhibit differing selectivity and affinity to galectins depending on the choice of 3-O-substitution.


Assuntos
Carboidratos/química , Galectina 1/química , Galectina 3/química , Galectinas/química , Tiogalactosídeos/química , Galactose , Galectina 1/metabolismo , Galectina 3/metabolismo , Galectinas/metabolismo , Humanos , Modelos Moleculares
9.
Cell Physiol Biochem ; 54(2): 287-302, 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32246616

RESUMO

BACKGROUND/AIMS: Galectin 3 (GAL-3) is a beta galactoside binding lectin that has different roles in normal and pathophysiological conditions. GAL-3 has been associated with heart failure and was linked to increased risk of death in a number of studies. GAL-3 was found to be up regulated in animal models of heart failure as well as myocardial infarction (MI). The objective of his study is to test if high GAL-3 after myocardial infarction has a protective role on the heart through its anti-apoptotic and anti-necrotic functions. METHODS: Male C57B6/J mice and GAL-3 knockout (KO) mice were used for permanent ligation of the left anterior descending artery of the heart to create infarction in the anterior myocardium. Heart and plasma samples were collected 24 hours after the induction of MI and were used for immunohistochemistry, Tunnel procedure, electron microscopy and enzyme linked immunosorbent assay (ELISA). RESULTS: Our results show that the significant increase in GAL-3 levels in the left ventricle at 24-hour following MI is associated with significant lower levels of pro-apoptotic proteins; cytochrome c, Bax, annexin V, cleaved caspase-3 and a higher levels of anti-apoptotic protein Bcl2 in GAL-3 wild MI group than GAL-3 KO group. We also have identified the anti-apoptotic activity of GAL-3 is mediated through a significant increase in Akt-1, NF kappa-B and beta- catenin proteins. In addition, we have identified the antiapoptotic activity is mediated through a significant lower levels of cathepsin-D protein. CONCLUSION: We conclude that the increased levels of GAL-3 at 24-hour following MI regulate antiapoptotic mechanisms in the myocardium that will shape the future course of the disease. We also identified that the anti-apoptotic mechanisms are likely mediated through interaction of GAL-3 with Akt-1, NF kappa-B, beta- catenin and cathepsin D proteins.


Assuntos
Apoptose/genética , Caspase 3/metabolismo , Galectina 3/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Anexina A5/metabolismo , Catepsinas/metabolismo , Citocromos c/metabolismo , Modelos Animais de Doenças , Galectina 3/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/ultraestrutura , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , beta Catenina/metabolismo
10.
Am J Physiol Heart Circ Physiol ; 318(5): H1068-H1079, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32216615

RESUMO

The clinical risks and prognosis of diabetic vascular intimal calcification (VIC) and medial calcification (VMC) are different. This study aims to investigate the mechanism of VIC/VMC translocation. Anterior tibial arteries were collected from patients with diabetic foot amputation. The patients were then divided into VIC and VMC groups. There were plaques in all anterior tibial arteries, while the enrichment of galectin-3 in arterial plaques in the VIC group was significantly higher than that in the VMC group. Furthermore, a macrophage/vascular smooth muscle cell (VSMC) coculture system was constructed. VSMC-derived extracellular vesicles (EVs) was labeled with fluorescent probe. After macrophages were pretreated with recombinant galectin-3 protein, the migration of VSMC-derived EVs and VSMC-derived calcification was more pronounced. And anti-galectin-3 antibody can inhibit this process of EVs and calcification translocation. Then, lentivirus (LV)-treated bone marrow cells (BMCs) were transplanted into apolipoprotein E-deficient (ApoE-/-) mice, and a diabetic atherosclerosis mouse model was constructed. After 15 wk of high-fat diet, ApoE-/- mice transplanted with LV-shgalectin-3 BMCs exhibited medial calcification and a concentrated distribution of EVs in the media. In conclusion, upregulation of galectin-3 in macrophages promotes the migration of VSMC-derived EVs to the intima and induces diabetic vascular intimal calcification.NEW & NOTEWORTHY The clinical risk and prognosis of vascular intimal and medial calcification are different. Macrophage galectin-3 regulates the migration of vascular smooth muscle cell-derived extracellular vesicles and mediates diabetic vascular intimal/medial calcification translocation. This study may provide insights into the early intervention in diabetic vascular calcification.


Assuntos
Angiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Galectina 3/metabolismo , Macrófagos/metabolismo , Túnica Íntima/metabolismo , Calcificação Vascular/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Apolipoproteínas E/genética , Células Cultivadas , Angiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/patologia , Vesículas Extracelulares/metabolismo , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Artérias da Tíbia/metabolismo , Artérias da Tíbia/patologia , Túnica Íntima/patologia , Calcificação Vascular/patologia
11.
PLoS One ; 15(3): e0229462, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32119722

RESUMO

Aging is a major risk factor for morbidity and mortality from cardiovascular causes in men. To better understand the cellular processes related to age-related cardiac complications, we undertook research aimed at comparative evaluation of genes expression and distribution of ß-catenin, CacyBP/SIP, galectin-3 and LMP7 in the heart of healthy men in different age groups. The study was conducted on the hearts of 12 men (organ donors) without a history of cardiovascular disease, who were divided into two age groups: men under and men over 45 years of age. On paraffin sections, immunohistochemical reactions were performed to detect ß-catenin, CacyBP/SIP, galectin-3 and immunoproteasome subunit LMP7. The expression of genes coding ß-catenin, CacyBP/SIP, galectin-3 and LMP7 was also evaluated by real-time PCR method. In the heart of men over 45 years old, both gene expression and immunoreactivity of ß-catenin, CacyBP/SIP, galectin-3 and LMP7 were stronger compared to younger individuals. The results of the presented studies suggest that ß-catenin, CacyBP/SIP, galectin-3 and immunoproteasomes might be involved in the internal regulation of heart homeostasis during ageing.


Assuntos
Envelhecimento/genética , Proteínas de Ligação ao Cálcio/genética , Galectina 3/genética , Miocárdio/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , beta Catenina/genética , Adulto , Distribuição por Idade , Idoso , Envelhecimento/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Galectina 3/metabolismo , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Complexo de Endopeptidases do Proteassoma/metabolismo , Regulação para Cima , Adulto Jovem , beta Catenina/metabolismo
12.
J Immunol Res ; 2020: 5284728, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149158

RESUMO

Atherosclerosis is a multifactorial chronic inflammatory arterial disease forming the pathological basis of many cardiovascular diseases such as coronary heart disease, heart failure, and stroke. Numerous studies have implicated inflammation as a key player in the initiation and progression of atherosclerosis. Galectin-3 (Gal-3) is a 30 kDa ß-galactose, highly conserved and widely distributed intracellularly and extracellularly. Gal-3 has been demonstrated in recent years to be a novel inflammatory factor participating in the process of intravascular inflammation, lipid endocytosis, macrophage activation, cellular proliferation, monocyte chemotaxis, and cell adhesion. This review focuses on the role of Gal-3 in atherosclerosis and the mechanism involved and several classical Gal-3 agonists and antagonists in the current studies.


Assuntos
Aterosclerose/etiologia , Aterosclerose/metabolismo , Suscetibilidade a Doenças , Galectina 3/metabolismo , Animais , Aterosclerose/epidemiologia , Aterosclerose/patologia , Biomarcadores , Modelos Animais de Doenças , Endotélio/metabolismo , Células Espumosas/imunologia , Células Espumosas/metabolismo , Células Espumosas/patologia , Galectina 3/química , Galectina 3/genética , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Estresse Oxidativo
13.
Nat Commun ; 11(1): 1229, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144274

RESUMO

Liquid-liquid phase separation (LLPS) explains many intracellular activities, but its role in extracellular functions has not been studied to the same extent. Here we report how LLPS mediates the extracellular function of galectin-3, the only monomeric member of the galectin family. The mechanism through which galectin-3 agglutinates (acting as a "bridge" to aggregate glycosylated molecules) is largely unknown. Our data show that its N-terminal domain (NTD) undergoes LLPS driven by interactions between its aromatic residues (two tryptophans and 10 tyrosines). Our lipopolysaccharide (LPS) micelle model shows that the NTDs form multiple weak interactions to other galectin-3 and then aggregate LPS micelles. Aggregation is reversed when interactions between the LPS and the carbohydrate recognition domains are blocked by lactose. The proposed mechanism explains many of galectin-3's functions and suggests that the aromatic residues in the NTD are interesting drug design targets.


Assuntos
Aglutinação , Galectina 3/metabolismo , Proteínas Intrinsicamente Desordenadas/metabolismo , Agregados Proteicos , Glicosilação , Lipopolissacarídeos/metabolismo , Micelas , Domínios Proteicos
14.
Biomed Res Int ; 2020: 4150735, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190664

RESUMO

Objective: The aim of this study was to investigate the expression of Snail, galectin-3, and IGF1R in benign and malignant pheochromocytoma and paraganglioma (PPGL) and explore their role in the diagnosis of malignant PPGL. Methods: We retrospectively collected and analyzed surgical tumor tissue from 226 patients initially diagnosed with PPGL who underwent surgery from Jan. 2009 to Jan. 2016 at West China Hospital, Sichuan University. We observed and quantified the expression of Snail, galectin-3, and IGF1R in paraffin-embedded samples by immunohistochemical staining. Results: The significant difference in survival time among the three groups (benign PHEO, benign PGL, and potentially malignant PPGL) was compared by Kaplan-Meier survival analysis. The positive staining of Snail, galectin-3, and IGF1R in the benign PHEO group was significantly lower than that in the other three groups (P < 0.001). The Kaplan-Meier survival plots indicated that the survival time of the patients with intense positive staining was significantly lower than that of the patients with weak positive staining. Conclusion: The intense expression of Snail, galectin-3, and IGF1R may be valuable indicators for the diagnosis of malignant PPGL.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Biomarcadores Tumorais/metabolismo , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Receptor IGF Tipo 1/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Idoso , China , Diagnóstico Diferencial , Feminino , Galectina 3/metabolismo , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paraganglioma/metabolismo , Paraganglioma/cirurgia , Feocromocitoma/metabolismo , Feocromocitoma/cirurgia , Estudos Retrospectivos , Software
15.
Carbohydr Res ; 490: 107903, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32171073

RESUMO

This study intends to investigate the inhibitory potential of different plant derived saccharides on cell migration and adhesion of pancreatic ductal adenocarcinoma (PDAC) cells to microvascular liver endothelium, particularly considering the role of transmembranous galectin-3. PDAC cell lines PancTu1 and Panc1 were characterized by considerable (transmembranous) galectin-3 (Gal3) expression. SiRNA mediated Gal3 knockdown as well as treatment with differentially processed pectins and arabinogalactan-proteins (AGPs) did not impact on cell migration of either PDAC cell line. In contrast, Gal3 knockdown reduced adhesion of PDAC cells to the liver endothelial cell line TMNK-1 being more pronounced in Panc1 cells. Similarly, plant derived substances did not impact cell adhesion of PancTu1 cells while partially hydrolyzed citrus pectin (MCP), pectinase-treated MCP (MCPPec) and partially hydrolized AGP (AGPTFA) clearly diminished adhesive properties of Panc1 cells. MCPPec or AGPTFA could not further intensify the adhesion reducing effect of galectin-3 knockdown, indicating that these plant derived polysaccharides are able to inhibit PDAC cell adhesion to liver endothelial cells in a galectin-3 dependent manner. Overall, these data suggest an inhibitory potential of plant derived processed saccharides which have undergone chemical modification in impairing PDAC cell adhesion to liver endothelium.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Citrus/química , Galectina 3/metabolismo , Mucoproteínas/farmacologia , Neoplasias Pancreáticas/metabolismo , Pectinas/farmacologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Galectina 3/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Metástase Neoplásica , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Proteínas de Plantas/farmacologia
16.
Diabetes Res Clin Pract ; 161: 108082, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32057966

RESUMO

INTRODUCTION: To assess the potential of galectin-3 and growth differentiation factor-15 (GDF-15) biomarkers for the early detection of diabetic kidney disease (DKD). METHODOLOGY: This was a cross-sectional study conducted over a period of 1.2 years. Patients were stratified based on estimated glomerular filtration rate (eGFR) and albuminuria level. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potential of biomarkers. RESULTS: A total of 90 patients included in this study. Patients were grouped as normoalbuminuria (30 patients), microalbuminuria (30 patients), and macroalbuminuria (30 patients). Galectin-3 and GDF-15 levels were significantly elevated in T2DM patients with macroalbuminuria (p = <0.05). Higher levels of galectin-3 and GDF-15 were found in patients with poor kidney function (Stage IV-V CKD). Negative correlation was observed between galectin- 3 (r = -0.472) and eGFR (p = 0.000), GDF-15 (r = -0.917) and eGFR (p <0.000). The ROC analysis yielded an area under curve (AUC) of 0.776 (95% CI: 0.677 to 0.875; p = <0.0001) for galectin-3 and an AUC of 0.963 (95% CI: 0.929 to 0.997; p = <0.0001) for GDF-15. CONCLUSION: In DKD patients the galectin-3 and GDF-15 levels were inversely related to the eGFR which was further confirmed by the ROC curve demonstrating the potential of galectin-3 and GDF-15 as a biomarker.


Assuntos
Biomarcadores/metabolismo , Nefropatias Diabéticas/diagnóstico , Galectina 3/metabolismo , Taxa de Filtração Glomerular/imunologia , Fator 15 de Diferenciação de Crescimento/metabolismo , Rim/patologia , Idoso , Estudos Transversais , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Mar Drugs ; 18(2)2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033203

RESUMO

The mucus of fish skin plays a vital role in innate immune defense. Some mucus proteins have the potential to incapacitate pathogens and/or inhibit their passage through the skin. In this study the aim was to isolate and characterize galectin(s), ß-galactosides binding proteins, present in skin mucus. A novel short form of galectin-3 was isolated from Atlantic salmon skin mucus by α-lactose agarose based affinity chromatography followed by Sephadex G-15 gel filtration. Mass spectrometric analysis showed that the isolated protein was the C-terminal half of galectin-3 (galectin-3C). Galectin-3C showed calcium independent and lactose inhabitable hemagglutination, and agglutinated the Gram-negative pathogenic bacteria Moritella viscosa. Galectin-3 mRNA was highly expressed in skin and gill, followed by muscle, hindgut, spleen, stomach, foregut, head kidney, and liver. Moritella viscosa incubated with galectin-3C had a modified proteome. Proteins with changed abundance included multidrug transporter and three ribosomal proteins L7/12, S2, and S13. Overall, this study shows the isolation and characterization of a novel galectin-3 short form involved in pathogen recognition and modulation, and hence in immune defense of Atlantic salmon.


Assuntos
Galectina 3/imunologia , Galectina 3/metabolismo , Moritella/efeitos dos fármacos , Muco/metabolismo , Aglutinação , Animais , Proteínas de Transporte , Proteínas de Peixes , Galectina 3/genética , Bactérias Gram-Negativas/efeitos dos fármacos , Imunidade Inata , Peptídeos , Domínios e Motivos de Interação entre Proteínas , Proteoma , Salmo salar/metabolismo , Pele/metabolismo
18.
Blood ; 135(14): 1146-1160, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32040544

RESUMO

Increasing evidence suggests that platelets play a predominant role in colon and breast cancer metastasis, but the underlying molecular mechanisms remain elusive. Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin that triggers platelet activation through immunoreceptor tyrosine-based activation motif (ITAM) signaling and thereby regulates diverse functions, including platelet adhesion, aggregation, and procoagulant activity. GPVI has been proposed as a safe antithrombotic target, because its inhibition is protective in models of arterial thrombosis, with only minor effects on hemostasis. In this study, the genetic deficiency of platelet GPVI in mice decreased experimental and spontaneous metastasis of colon and breast cancer cells. Similar results were obtained with mice lacking the spleen-tyrosine kinase Syk in platelets, an essential component of the ITAM-signaling cascade. In vitro and in vivo analyses supported that mouse, as well as human GPVI, had platelet adhesion to colon and breast cancer cells. Using a CRISPR/Cas9-based gene knockout approach, we identified galectin-3 as the major counterreceptor of GPVI on tumor cells. In vivo studies demonstrated that the interplay between platelet GPVI and tumor cell-expressed galectin-3 uses ITAM-signaling components in platelets and favors the extravasation of tumor cells. Finally, we showed that JAQ1 F(ab')2-mediated inhibition of GPVI efficiently impairs platelet-tumor cell interaction and tumor metastasis. Our study revealed a new mechanism by which platelets promote the metastasis of colon and breast cancer cells and suggests that GPVI represents a promising target for antimetastatic therapies.


Assuntos
Plaquetas/patologia , Neoplasias da Mama/patologia , Neoplasias do Colo/patologia , Galectina 3/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Animais , Plaquetas/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Neoplasias do Colo/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Metástase Neoplásica/patologia , Ativação Plaquetária , Glicoproteínas da Membrana de Plaquetas/genética , Mapas de Interação de Proteínas
19.
Dev Cell ; 52(1): 69-87.e8, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31813797

RESUMO

Endomembrane damage elicits homeostatic responses including ESCRT-dependent membrane repair and autophagic removal of damaged organelles. Previous studies have suggested that these systems may act separately. Here, we show that galectin-3 (Gal3), a ß-galactoside-binding cytosolic lectin, unifies and coordinates ESCRT and autophagy responses to lysosomal damage. Gal3 and its capacity to recognize damage-exposed glycans were required for efficient recruitment of the ESCRT component ALIX during lysosomal damage. Both Gal3 and ALIX were required for restoration of lysosomal function. Gal3 promoted interactions between ALIX and the downstream ESCRT-III effector CHMP4 during lysosomal repair. At later time points following lysosomal injury, Gal3 controlled autophagic responses. When this failed, as in Gal3 knockout cells, lysosomal replacement program took over through TFEB. Manifestations of this staged response, which includes membrane repair, removal, and replacement, were detected in model systems of lysosomal damage inflicted by proteopathic tau and during phagosome parasitism by Mycobacterium tuberculosis.


Assuntos
Autofagia , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Galectina 3/metabolismo , Membranas Intracelulares/metabolismo , Lisossomos/metabolismo , Tuberculose/prevenção & controle , Proteínas tau/metabolismo , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Glicosilação , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/patogenicidade , Tuberculose/imunologia , Tuberculose/metabolismo , Tuberculose/microbiologia
20.
Mol Cell Biochem ; 464(1-2): 143-152, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31782085

RESUMO

Heart failure (HF) is considered one of the most common diseases and one of the major causes of death. The latest studies show that HF is associated with an increase in oxidative stress. The use of antioxidants as therapy is effective in animal models, but not in humans. In this review, we analyse some emerging markers related to oxidative stress, evaluating their possible use as therapeutic targets: galectin-3, a ß galactoside associated with myocardial fibrosis, α1-antitrypsin, an antiprotease and lectin-like oxidized low-density-lipoprotein receptor-1, the major receptor for ox-LDL. The up-regulation of galectin-3 appears to be associated with HF, atrial fibrillation, dilated cardiomyopathy, fibrogenesis and mortality, while in other cases it seems that galectin-3 may be protective in ischaemia-reperfusion injury. Serum α1-antitrypsin protein levels may increase in the presence of high concentrations of serum proteases, which are over expressed during reperfusion. The overexpression of α1-antitrypsin or the exogenous α1-antitrypsin treatment exhibits an anti-oxidative stress role, evaluated by increased eNOS expression and by decreased MMP9 expression, implicated in HF. The cardiac lectin-like oxidized low-density-lipoprotein receptor-1 is activated by oxidative stress in ischaemia-reperfusion injury, inducing apoptosis in cardiomyocytes through the deleterious NF-kB pathway, while the administration of anti-lectin-like oxidized low-density-lipoprotein receptor-1 antibody suppresses apoptosis and reduces the extent of myocardial infarction. In conclusion, α1-antitrypsin and lectin-like oxidized low-density-lipoprotein receptor-1 seem to represent two good markers in HF and therapeutic targets, whereas galectin-3 does not.


Assuntos
Galectina 3/metabolismo , Insuficiência Cardíaca/metabolismo , Infarto do Miocárdio/metabolismo , Estresse Oxidativo , Receptores Depuradores Classe E/metabolismo , alfa 1-Antitripsina/metabolismo , Apoptose , Biomarcadores/metabolismo , Insuficiência Cardíaca/patologia , Humanos , Infarto do Miocárdio/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...