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.

scholarly journals Rac1 promotes TGF-β-stimulated mesangial cell type I collagen expression through a PI3K/Akt-dependent mechanism

2009 ◽  
Vol 297 (5) ◽  
pp. F1316-F1323 ◽  
Author(s):  
Susan C. Hubchak ◽  
Erin E. Sparks ◽  
Tomoko Hayashida ◽  
H. William Schnaper
Keyword(s):  
Promoter Activity ◽  
Type I Collagen ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Signal Propagation ◽  
Type I ◽  
Human Mesangial Cells ◽  
Collagen Expression ◽  
Pi3k Activity ◽  
Tgf Β1

Transforming growth factor (TGF)-β is a central mediator in the progression of glomerulosclerosis, leading to accumulation of aberrant extracellular matrix proteins and inappropriate expression of smooth muscle α-actin in the kidney. Previously, we reported that disrupting the cytoskeleton diminished TGF-β-stimulated type I collagen accumulation in human mesangial cells. As cytoskeletal signaling molecules, including the Rho-family GTPases, have been implicated in fibrogenesis, we sought to determine the respective roles of RhoA and Rac1 in HMC collagen I expression. TGF-β1 activated both RhoA and Rac1 within 5 min of treatment, and this activation was dependent on the kinase activity of the type I TGF-β receptor. TGF-β1-stimulated induction of type I collagen mRNA expression and promoter activity was diminished by inhibiting Rac1 activity and was increased by a constitutively active Rac1 mutant, whereas inhibiting RhoA activity had no such effect. Rac1 activation required phosphatidylinositol-3-kinase (PI3K) activity. Furthermore, the PI3K antagonist, LY294002, reduced TGF-β1-stimulated COL1A2 promoter activity and Rac1 activation. It also partially blocked active Rac1-stimulated collagen promoter activity, suggesting that PI3K activity contributes to both TGF-β activation of Rac1 and signal propagation downstream of Rac1. Thus, while both Rac1 and RhoA are rapidly activated in response to TGF-β1 in human mesangial cells, only Rac1 activation enhances events that contribute to mesangial cell collagen expression, through a positive feedback loop involving PI3K.

Glycated albumin stimulation of PKC-β activity is linked to increased collagen IV in mesangial cells

1999 ◽  
Vol 276 (5) ◽  
pp. F684-F690 ◽  
Author(s):  
Margo P. Cohen ◽  
Fuad N. Ziyadeh ◽  
Gregory T. Lautenslager ◽  
Jonathan A. Cohen ◽  
Clyde W. Shearman
Keyword(s):  
Collagen Type ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Glycated Albumin ◽  
Matrix Proteins ◽  
Collagen Type Iv ◽  
Type Iv ◽  
Pkc Β ◽  
Tgf Β1 ◽  
Stimulation Of

Albumin modified by Amadori-glucose adducts induces coordinate increases in the expression of extracellular matrix proteins, transforming growth factor (TGF)-β1, and the TGF-β type II receptor in glomerular mesangial cells. Because activation of protein kinase C (PKC) accompanies the increased mesangial cell expression of matrix proteins and TGF-β1 induced by high ambient glucose, we postulated that glycated albumin (GA) modulates PKC activity and that PKC participates in mediating the GA-induced stimulation of matrix production. To test this hypothesis, we examined the effects of PKC inhibitors on collagen type IV production by mouse or rat mesangial cells incubated with GA, and the influence of GA on PKC activity in these cells. Increased collagen type IV production evoked by GA in 5.5 and 25 mM glucose in mouse mesangial cells was prevented by both general (GF-109203X) and β-specific (LY-379196) PKC inhibitors. Total PKC activity, measured by phosphorylation of a PKC-specific substrate, increased with time after exposure of rat mesangial cells to GA compared with the nonglycated, glucose-free counterpart. GA caused an increase in PKC-β1 membrane-bound fraction and in total PKC activity in media containing physiological (5.5 mM) glucose concentrations in rat mesangial cells, confirming that the glucose-modified protein, and not a “hyperglycemic” milieu, was responsible. The findings indicate that Amadori-modified albumin stimulates mesangial cell PKC activity, and that activation of the PKC-β isoform is linked to the stimulation of collagen type IV production.

scholarly journals High glucose and TGF-β1 reduce expression of endoplasmic reticulum-resident selenoprotein S and selenoprotein N in human mesangial cells

Renal Failure ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 762-769
Author(s):  
Fumeng Huang ◽  
Yuanxu Guo ◽  
Li Wang ◽  
Lanmei Jing ◽  
Zhao Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
High Glucose ◽  
Mesangial Cells ◽  
Human Mesangial Cells ◽  
Selenoprotein S ◽  
Tgf Β1

scholarly journals TGF-β1 activates MAP kinase in human mesangial cells: A possible role in collagen expression

1999 ◽  
Vol 56 (5) ◽  
pp. 1710-1720 ◽  
Author(s):  
Tomoko Hayashida ◽  
Anne-Christine Poncelet ◽  
Susan C. Hubchak ◽  
H. William Schnaper
Keyword(s):  
Map Kinase ◽  
Mesangial Cells ◽  
Human Mesangial Cells ◽  
Collagen Expression ◽  
Tgf Β1

scholarly journals Plasma Gelsolin Promotes Proliferation of Mesangial Cell in IgA Nephropathy

2016 ◽  
Vol 40 (6) ◽  
pp. 1473-1486 ◽  
Author(s):  
Lei Zhang ◽  
Dan Kong ◽  
Hongxue Meng ◽  
Changsong Han ◽  
Jiang Zhu ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Transforming Growth Factor ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Clinical Symptoms ◽  
Critical Role ◽  
Renal Tissue ◽  
Actin Binding ◽  
Plasma Gelsolin ◽  
Tgf Β1

Background/Aims: Plasma gelsolin (pGSN) is an actin-binding protein that plays a critical role in the pathogenesis of rheumatoid arthritis. However, whether pGSN is involved in other immunological diseases remains unknown. This study focused on the relationship between pGSN and immunoglobulin A (IgA) nephropathy (IgAN). Methods: Two hundred patients with IgAN, 200 patients each with several other types of nephropathy and healthy controls (HCs) who underwent kidney biopsies between 2000 and 2014 were enrolled in the study. The Oxford classification system was used to predict the risk of disease progression. Serum and renal tissue were used to detect pGSN, and the correlations between pGSN and IgA, galactose-deficient IgA1 (Gd-IgA1), transforming growth factor beta1 (TGF-β1), fibronectin (FN) content, clinical symptoms, and kidney function were analyzed. Results: We found that the pGSN levels were significantly decreased in sera from IgAN patients compared to sera from patients with other forms of glomerular nephritis and HCs. Furthermore, the serum pGSN levels were negatively correlated with the serum IgA1, FN, and TGF-β1 levels, and positively correlated with the estimated glomerular filtration rate. Conversely, the glomerular pGSN content was significantly elevated in the IgAN patients and was positively correlated with TGF-β1 and FN levels. In renal tissue, the pGSN levels were significantly higher in IgAN patients with M1 and S1 compared to patients with M0 and S0 (p < 0.05). Meanwhile, pGSN promoted human mesangial cell (HMC) proliferation by facilitating cell mitosis in vitro. pGSN also promoted integrin α2β1 expression in HMCs and enhanced the integrin α2β1-pGSN interaction. Conclusion: Our study suggested that pGSN may play an important role in the development of IgAN by promoting the proliferation of mesangial cells and that serum and glomerular pGSN levels may be new markers for predicting IgAN progression and prognosis.

scholarly journals Regulation of cultured human mesangial cell growth by ionized macromolecules.

1992 ◽  
Vol 2 (10) ◽  
pp. S95
Author(s):  
F Pugliese ◽  
G A Cinotti ◽  
P Menè
Keyword(s):  
Cell Growth ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Fetal Bovine Serum ◽  
Inhibitory Effect ◽  
The Other ◽  
Net Charge ◽  
Human Mesangial Cells ◽  
Human Mesangial Cell ◽  
Fetal Bovine

We evaluated the importance of the net charge of polyionic macromolecules in the regulation of cultured human mesangial cell growth. Structurally unrelated polyanionic compounds, i.e., heparin, suramin, poly-L-aspartic acid, and poly-L-glutamic acid, strongly inhibited 10% fetal bovine serum-stimulated cell proliferation. On the other hand, two polycations, protamin sulfate and poly-L-lysine, were equally effective in inhibiting cell growth. The antiproliferative activity of each compound was neutralized by molecules with opposite net charge. These data indicate that both anionic and cationic macromolecules exert an antimitogenic effect on cultured human mesangial cells. This inhibitory effect is dependent upon charge density rather than on the net electric charge of each compound.

scholarly journals Smooth-Muscle Calponin in Mesangial Cells: Regulation of Expression and a Role in Suppressing Glomerulonephritis

2002 ◽  
Vol 13 (2) ◽  
pp. 322-331 ◽  
Author(s):  
Youichi Sugenoya ◽  
Ashio Yoshimura ◽  
Hisako Yamamura ◽  
Kiyoko Inui ◽  
Hiroyuki Morita ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Actin Binding ◽  
Luciferase Reporter ◽  
Tnf Α ◽  
Mesangial Cell Proliferation ◽  
Tgf Β1

ABSTRACT. The basic or h1 calponin gene, which encodes an actin-binding protein involved in the regulation of smooth-muscle shortening velocity, is known to be a smooth-muscle differentiation-specific gene. It was found that basic calponin was expressed by cultured mesangial cells and localized along the actin filaments. Among the growth factors involved in the mesangial cell pathophysiology, including platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor–α (TNF-α), and transforming growth factor–β1 (TGF-β1), TNF-α potently downregulates basic calponin expression in both the mRNA and protein levels, whereas TGF-β1 upregulates the calponin expression. PDGF-BB also reduced its mRNA expression. The half-life of basic calponin mRNA was determined to be similar between TNF-α–treated and –untreated mesangial cells, whereas cell transfection assays that used a luciferase reporter gene construct containing the functional basic calponin promoter showed that TNF-α and PDGF-BB reduced the transcriptional activity. Because stimulation with TNF-α and PDGF-BB was associated with mesangial cell proliferation, basic calponin may play a role in the suppression of mesangial cell proliferation. Treatment with anti–glomerular basement membrane antibody in calponin knockout mice induced more severe nephritis than in wild type mice, as judged from an increase in the urinary protein excretion, glomerular cellularity, and number of proliferating cell nuclear antigen–positive cells in glomerulus. These results suggest that basic calponin expression may serve as one of the intrinsic regulators of glomerular nephritis. Elucidation of the molecular mechanisms for regulation of the basic calponin expression in mesangial cells may improve the understanding of the molecular basis and pathogenesis of the glomerular response to injury.

scholarly journals Suppressor of cytokine signaling-1 reduces high glucose-induced TGF-β1 and fibronectin synthesis in human mesangial cells

FEBS Letters ◽  
2008 ◽  
Vol 582 (23-24) ◽  
pp. 3484-3488 ◽  
Author(s):  
Yonghong Shi ◽  
Yanling Zhang ◽  
Chen Wang ◽  
Chunyang Du ◽  
Song Zhao ◽  
...  
Keyword(s):  
High Glucose ◽  
Mesangial Cells ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Human Mesangial Cells ◽  
Tgf Β1
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