scholarly journals CCN3 suppresses TGF-β1-induced extracellular matrix accumulation in human mesangial cells in vitro

2017 ◽  
Vol 39 (2) ◽  
pp. 222-229 ◽  
Author(s):  
Hai-fei Liu ◽  
Hong Liu ◽  
Lin-li Lv ◽  
Kun-ling Ma ◽  
Yi Wen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mesangial Cells ◽  
Human Mesangial Cells ◽  
Matrix Accumulation ◽  
Tgf Β1

scholarly journals Transforming Growth Factor-β Is a Potent Inhibitor of Extracellular Matrix Degradation by Cultured Human Mesangial Cells

1999 ◽  
Vol 10 (4) ◽  
pp. 790-795 ◽  
Author(s):  
WILLIAM H. BARICOS ◽  
SHIRLEY L. CORTEZ ◽  
MICHAEL DEBOISBLANC ◽  
SHI XIN
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Renal Disease ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Potent Inhibitor ◽  
Matrix Degradation ◽  
Human Mesangial Cells ◽  
Ecm Degradation ◽  
Tgf Β1

Abstract. Accumulation of the glomerular extracellular matrix (ECM) is a pivotal event in the progression from acute glomerular injury to end-stage renal disease. Although enhanced ECM synthesis has been demonstrated to contribute to ECM accumulation, the role of decreased ECM degradation is largely unknown. It was previously shown that glomerular ECM degradation is mediated by a plasminogen activator (PA)/plasmin/matrix metalloproteinase 2 (MMP-2) cascade. However, little information is available regarding the factors that regulate the activity of this degradative cascade in normal or pathologic states. Transforming growth factor-β1 (TGF-β1) is shown here to be a potent inhibitor of ECM degradation by cultured human mesangial cells. Using human mesangial cells grown on thin films of 125I-labeled Matrigel, dose-dependent inhibition of ECM degradation in the presence of TGF-β1 was observed, reaching >90% inhibition with 0.4 ng/ml TGF-β1. Addition of anti-TGF-β antibodies (4 μg/ml) in the absence of exogenous TGF-β increased ECM degradation (1.8 ± 0.2-fold versus controls, P < 0.05). In contrast, platelet-derived growth factor, at concentrations up to 10 ng/ml, had no effect on ECM degradation. TGF-β completely blocked the conversion of plasminogen to plasmin and markedly reduced the conversion of latent MMP-2 to active MMP-2. TGF-β did not significantly alter the levels of tissue PA, total MMP-2, or tissue inhibitor of metalloproteinase-1, but did increase the levels of PA inhibitor-1 (1.8-fold, P < 0.05), the major physiologic inhibitor of PA. These data document that TGF-β is a potent inhibitor of ECM degradation by cultured human mesangial cells, and they suggest that decreased mesangial matrix degradation, caused by TGF-β-mediated decreases in the activity of the PA/plasmin/MMP-2 cascade, may contribute to the glomerular matrix accumulation that occurs in progressive renal disease.

scholarly journals Inactivation of AMPK Mediates High Phosphate-Induced Extracellular Matrix Accumulation via NOX4/TGFß-1 Signaling in Human Mesangial Cells

2014 ◽  
Vol 34 (4) ◽  
pp. 1260-1272 ◽  
Author(s):  
Alexandros Papadimitriou ◽  
Elisa B.M.I. Peixoto ◽  
Kamila C. Silva ◽  
Jacqueline M. Lopes de Faria ◽  
José B. Lopes de Faria
Keyword(s):  
Extracellular Matrix ◽  
Mesangial Cells ◽  
Human Mesangial Cells ◽  
Matrix Accumulation ◽  
High Phosphate

scholarly journals Ergosterol Ameliorates Diabetic Nephropathy by Attenuating Mesangial Cell Proliferation and Extracellular Matrix Deposition via the TGF-β1/Smad2 Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 483 ◽  
Author(s):  
Zhonghua Dong ◽  
Yueyue Sun ◽  
Guangwei Wei ◽  
Siying Li ◽  
Zhongxi Zhao
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Diabetic Mice ◽  
Mesangial Cell Proliferation ◽  
Tgf Β1

(1) Background: Diabetic nephropathy, a microvascular complication of diabetes, is one of the principal causes of end-stage renal disease worldwide. The aim of this study was to explore the therapeutic effects of ergosterol on diabetic nephropathy. (2) Methods: Streptozotocin (STZ)-induced C57BL/6 diabetic mice were treated with ergosterol (10, 20, 40 mg/kg/day) for 8 weeks by oral gavage. The in vitro study employed rat mesangial cells exposed to 30 mM glucose for 48 h in the presence of 10 or 20 μM ergosterol. (3) Results: Ergosterol treatment improved body weights, ameliorated the majority of biochemical and renal functional parameters and histopathological changes, and reduced extracellular matrix (ECM) deposition in diabetic mice. In vitro, ergosterol suppressed proliferation, reduced the levels of ECM proteins, and increased the expression of matrix metalloproteinase-2 and -9 in high glucose-induced mesangial cells; Furthermore, ergosterol markedly improved transforming growth factor-β1 (TGF-β1) expression, enhanced phosphorylation levels of drosophila mothers against decapentaplegic 2 (Smad2), and regulated the downstream factors in vivo and in vitro. (4) Conclusions: Ergosterol alleviated mesangial cell proliferation and the subsequent ECM deposition by regulating the TGF-β1/Smad2 signaling pathway.

Collagen I upregulates extracellular matrix gene expression and secretion of TGF-β1 by cultured human mesangial cells

2004 ◽  
Vol 286 (6) ◽  
pp. C1335-C1343 ◽  
Author(s):  
R. Ortega-Velazquez ◽  
M. Gonzalez-Rubio ◽  
M. P. Ruiz-Torres ◽  
M. L. Diez-Marques ◽  
M. C. Iglesias ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mrna Expression ◽  
Blot Analysis ◽  
Mesangial Cells ◽  
Phenotypic Expression ◽  
Renal Diseases ◽  
Type I ◽  
Human Mesangial Cells ◽  
Matrix Gene ◽  
Tgf Β1

Progressive renal diseases are characterized by an increased synthesis of extracellular matrix (ECM) components. The mechanisms involved in the development of these alterations are not completely known, but a crucial role for TGF-β1 has been suggested. Moreover, the ability of the ECM to modulate the phenotypic expression of different cell types has been widely described. In experiments presented here, human mesangial cells (HMC) were grown on collagen type I (COL I) or IV (COL IV). ECM protein and TGF-β1 mRNA expression were evaluated by Northern blot analysis, and TGF-β1 secretion was evaluated by ELISA. The involvement of tyrosine kinase and serine-threonine kinase pathways was studied by Western blot analysis, immunofluorescence, and in vitro kinase assays. HMC cultured on COL I showed an increased mRNA expression of COL I and COL IV, fibronectin, and TGF-β1. Both tyrosine phosphorylation and integrin-linked kinase (ILK) activity increased when HMC were cultured on COL I, and blockade of these pathways inhibited the increased secretion of TGF-β1. In conclusion, the present results support a role for extracellular COL I in the regulation of TGF-β1 synthesis during progressive renal sclerosis and fibrosis and the subsequent increase in newly synthesized ECM proteins. In addition, ILK, along with the tyrosine kinases, participates in the genesis of this effect.

scholarly journals Activation of transmembrane receptor tyrosine kinase DDR1-STAT3 cascade by extracellular matrix remodeling promotes liver metastatic colonization in uveal melanoma

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Wei Dai ◽  
Shenglan Liu ◽  
Shubo Wang ◽  
Li Zhao ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cancer Cells ◽  
Uveal Melanoma ◽  
Specific Inhibitor ◽  
Type I ◽  
Matrix Remodeling ◽  
Metastatic Colonization ◽  
Tgf Β1

AbstractColonization is believed a rate-limiting step of metastasis cascade. However, its underlying mechanism is not well understood. Uveal melanoma (UM), which is featured with single organ liver metastasis, may provide a simplified model for realizing the complicated colonization process. Because DDR1 was identified to be overexpressed in UM cell lines and specimens, and abundant pathological deposition of extracellular matrix collagen, a type of DDR1 ligand, was noted in the microenvironment of liver in metastatic patients with UM, we postulated the hypothesis that DDR1 and its ligand might ignite the interaction between UM cells and their surrounding niche of liver thereby conferring strengthened survival, proliferation, stemness and eventually promoting metastatic colonization in liver. We tested this hypothesis and found that DDR1 promoted these malignant cellular phenotypes and facilitated metastatic colonization of UM in liver. Mechanistically, UM cells secreted TGF-β1 which induced quiescent hepatic stellate cells (qHSCs) into activated HSCs (aHSCs) which secreted collagen type I. Such a remodeling of extracellular matrix, in turn, activated DDR1, strengthening survival through upregulating STAT3-dependent Mcl-1 expression, enhancing stemness via upregulating STAT3-dependent SOX2, and promoting clonogenicity in cancer cells. Targeting DDR1 by using 7rh, a specific inhibitor, repressed proliferation and survival in vitro and in vivo outgrowth. More importantly, targeting cancer cells by pharmacological inactivation of DDR1 or targeting microenvironmental TGF-β1-collagen I loop exhibited a prominent anti-metastasis effect in mice. In conclusion, targeting DDR1 signaling and TGF-β signaling may be a novel approach to diminish hepatic metastasis in UM.

scholarly journals Expression of extracellular matrix molecules in human mesangial cells in response to prolonged hyperglycaemia

1996 ◽  
Vol 316 (3) ◽  
pp. 985-992 ◽  
Author(s):  
Nadia Abdel WAHAB ◽  
Katherine HARPER ◽  
Roger M. MASON
Keyword(s):  
Cell Cultures ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Dermal Fibroblasts ◽  
Rt Pcr ◽  
Collagen Types ◽  
Human Mesangial Cells ◽  
Core Proteins ◽  
Cell Layers ◽  
Tgf Β1

Post-mitotic cultures of human mesangial cells were maintained in media containing 4–30 mM D-glucose for up to 28 days. Changes in mRNA and protein levels for specific macromolecules occurred between 7 and 14 days after initiating hyperglycaemic conditions. Slot blot analysis showed 2–3-fold increases in mRNAs for collagen type I, fibronectin, versican and perlecan, whereas mRNA for decorin was increased by up to 20-fold. Levels of mRNAs for biglycan and syndecan were unaffected by hyperglycaemic culture. Reverse transcriptase PCR (RT–PCR) confirmed that decorin mRNA levels are greatly elevated and also showed increased transcription of the TGF-β1 gene in hyperglycaemic cultures. Western analysis and ELISA indicated accumulations of collagen types I and III, laminin and fibronectin in the cell layers and media of hyperglycaemic cultures with increasing time. Type IV collagen did not accumulate in either compartment of hyperglycaemic mesangial cell cultures. Collagen types I, III, and fibronectin did not accumulate in the cell layers of hyperglycaemic human dermal fibroblasts, indicating a cell-specific response in mesangial cultures. Decorin and versican, but not biglycan, were increased in the hyperglycaemic mesangial cell culture media. There were no apparent changes in core proteins for decorin and biglycan in fibroblast media. Transforming growth factor β1 (TGF-β1) in hyperglycaemic mesangial cell cultures increased 5-fold after 7 days, but decreased thereafter to only approx. 2-fold after 28 days. The changes in TGF-β1 mRNA, as detected by RT–PCR, and protein followed one another closely.

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