Albumin modified by Amadori glucose adducts activates mesangial cell type IV collagen gene transcription

1995 ◽  
Vol 151 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Margo P. Cohen ◽  
Elizabeth Hud ◽  
Van-Yu Wu ◽  
Fuad N. Ziyadeh
Keyword(s):  
Gene Transcription ◽  
Type Iv Collagen ◽  
Mesangial Cell ◽  
Collagen Gene ◽  
Cell Type ◽  
Type Iv

Hypoxia and high glucose cause exaggerated mesangial cell growth and collagen synthesis: role of osteopontin

2001 ◽  
Vol 280 (4) ◽  
pp. F667-F674 ◽  
Author(s):  
Chhinder P. Sodhi ◽  
Sarojini A. Phadke ◽  
Daniel Batlle ◽  
Atul Sahai
Keyword(s):  
Cell Growth ◽  
High Glucose ◽  
Collagen Synthesis ◽  
Type Iv Collagen ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Neutralizing Antibody ◽  
Cell Number ◽  
Mrna Levels ◽  
Type Iv

The effect of hypoxia on the proliferation and collagen synthesis of cultured rat mesangial cells was examined under normal-glucose (NG, 5 mM) and high-glucose (HG, 25 mM)-media conditions. In addition, a role for osteopontin (OPN) in mediating these processes was assessed. Quiescent cultures were exposed to hypoxia (3% O2) and normoxia (18% O2) in a serum-free medium with NG or HG, and cell proliferation, collagen synthesis, and OPN expression were assessed. Cells exposed to hypoxia in NG medium resulted in significant increases in [3H]thymidine incorporation, cell number, and [3H]proline incorporation, respectively. HG incubations also produced significant stimulation of these parameters under normoxic conditions, which were markedly enhanced in cells exposed to hypoxia in HG medium. In addition, hypoxia and HG stimulated the mRNA levels of type IV collagen, and the combination of hypoxia and HG resulted in additive increases in type IV collagen expression. Hypoxia and HG also stimulated OPN mRNA and protein levels in an additive fashion. A neutralizing antibody to OPN or its β3-integrin receptor significantly blocked the effect of hypoxia and HG on proliferation and collagen synthesis. In conclusion, these results demonstrate for the first time that hypoxia in HG medium produces exaggerated mesangial cell growth and type IV collagen synthesis. In addition, OPN appears to play a role in mediating the accelerated mesangial cell growth and collagen synthesis found in a hyperglycemic and hypoxic environment.

Serum-stimulated α1 type IV collagen gene transcription is mediated by TGF-β and inhibited by estradiol

1998 ◽  
Vol 274 (2) ◽  
pp. F252-F258 ◽  
Author(s):  
Jun Lei ◽  
Sharon Silbiger ◽  
Fuad N. Ziyadeh ◽  
Joel Neugarten
Keyword(s):  
Growth Factor ◽  
Gene Transcription ◽  
Type Iv Collagen ◽  
Transforming Growth Factor ◽  
Combined Treatment ◽  
Calf Serum ◽  
Neutralizing Antibody ◽  
Transforming Growth Factor Β ◽  
Inhibitory Effect ◽  
Type Iv

We examined the hypothesis that fetal calf serum (FCS) stimulates murine mesangial cell α1 type IV collagen ( COL4A1) gene transcription by increasing autocrine production of transforming growth factor-β (TGF-β) through a platelet-derived growth factor (PDGF)-dependent mechanism. PDGF-stimulated COL4A1 gene transcription was inhibited by neutralizing antibody to TGF-β (119.3 ± 3.6 vs. 106.0 ± 6.2 relative luciferase units, expressed as a percentage of control untreated cells, P < 0.003). FCS-stimulated gene transcription was inhibited by neutralizing antibody to PDGF (148.3 ± 4.1 vs. 136.7 ± 0.3 relative luciferase units, P < 0.002) and by neutralizing antibody to TGF-β (148.3 ± 4.1 vs. 127.1 ± 3.4 relative luciferase units, P < 0.036). The inhibitory effect of combined treatment with anti-PDGF and anti-TGF-β antibody on gene transcription was no greater than that of anti-TGF-β antibody alone [129.5 ± 0.53 vs. 127.1 ± 3.4 relative luciferase units, P = not significant (NS)]. FCS-stimulated gene transcription was also inhibited by estradiol (10−7 M) (148.4 ± 3.1 vs. 119.4 ± 8.1 relative luciferase units, P < 0.019). In the presence of estradiol, anti-TGF-β antibody failed to further reduce serum-stimulated gene transcription (119.4 ± 8.1 vs. 115.6 ± 9.8, P = NS), suggesting that estradiol reverses FCS-stimulated COL4A1 gene transcription by antagonizing the actions of TGF-β. Measurement of type IV collagen synthesis by Western blotting confirmed that the intact gene responded in a manner analogous to the promoter construct.

Selective estrogen receptor modulators suppress mesangial cell collagen synthesis

2000 ◽  
Vol 279 (2) ◽  
pp. F309-F318 ◽  
Author(s):  
Joel Neugarten ◽  
Anjali Acharya ◽  
Jun Lei ◽  
Sharon Silbiger
Keyword(s):  
Estrogen Receptor ◽  
Collagen Synthesis ◽  
Type Iv Collagen ◽  
Mesangial Cell ◽  
Type I ◽  
Dependent Manner ◽  
Type Iv ◽  
Estrogen Receptor Modulators ◽  
Receptor Modulators ◽  
Dose Dependent

Estrogen receptor modulators (SERMs) are “designer drugs” that exert estrogen-like actions in some cells but not in others. We examined the effects of the SERMs LY-117018 (an analog of raloxifene) and tamoxifen on mesangial cells synthesis of type I and type IV collagen. We found that LY-117018 and tamoxifen suppressed mesangial cell type IV collagen gene transcription and type IV collagen protein synthesis in a dose-dependent manner, with a potency identical to that of estradiol. Type I collagen synthesis was also suppressed by LY-117018 in a dose-dependent manner with a potency identical to that of estradiol but greater than that of tamoxifen. Genistein, which selectively binds to estrogen receptor-β in nanomolar concentrations, suppressed type I and type IV collagen synthesis, suggesting that estrogen receptor-β mediates the effects of estrogen on collagen synthesis. Because matrix accumulation is central to the development of glomerulosclerosis, second-generation SERMs may prove clinically useful in ameliorating progressive renal disease without the adverse effects of estrogen on reproductive tissues.

Physiology and Cell Biology Update: Mechanisms of Type IV Collagen Gene Regulation

1991 ◽  
Vol 18 (1) ◽  
pp. 134-139 ◽  
Author(s):  
Leslie A. Bruggeman ◽  
Satoshi Horikoshi ◽  
Peter D. Burbelo ◽  
Yoshihiko Yamada ◽  
Paul E. Klotman
Keyword(s):  
Gene Regulation ◽  
Cell Biology ◽  
Type Iv Collagen ◽  
Collagen Gene ◽  
Type Iv

De novo expression of a type IV collagen gene in Drosophila embryos is restricted to mesodermal derivatives and occurs at germ band shortening

Development ◽  
1988 ◽  
Vol 102 (2) ◽  
pp. 369-376 ◽  
Author(s):  
C. Mirre ◽  
J.P. Cecchini ◽  
Y. Le Parco ◽  
B. Knibiehler
Keyword(s):  
Type Iv Collagen ◽  
De Novo ◽  
Collagen Gene ◽  
Visceral Mesoderm ◽  
Type Iv ◽  
Collagen Chain ◽  
Fat Bodies ◽  
Membrane Type ◽  
Gene Overlap

We have examined directly the expression of one collagen gene (DCg1) during Drosophila melanogaster embryogenesis by means of in situ hybridization. Transcripts of this gene, which were demonstrated to encode a basement membrane type IV collagen chain, began to accumulate specifically in mesodermal derivatives at stages 12–13 of embryogenesis, and not before. Cells expressing this gene overlap, or are closely intermingled with, somatic and visceral mesoderm in stages 12–14. In stages 15–17, in addition to the strongly positive fat bodies, highly labelled cell spots are found scattered around all the parts of the gut and symmetrically on each side of the ventral nerve cord. They correspond to circulating mesodermal cells which we consider to be haemocytes or mesoblasts.

scholarly journals Type IV Collagen and Laminin Regulate Glomerular Mesangial Cell Susceptibility to Apoptosis Via β1 Integrin-Mediated Survival Signals

1999 ◽  
Vol 155 (2) ◽  
pp. 599-606 ◽  
Author(s):  
Andrew Mooney ◽  
Kathryn Jackson ◽  
Rachel Bacon ◽  
Charles Streuli ◽  
Gwynneth Edwards ◽  
...  
Keyword(s):  
Type Iv Collagen ◽  
Mesangial Cell ◽  
Β1 Integrin ◽  
Glomerular Mesangial Cell ◽  
Type Iv ◽  
Survival Signals

miR-378 reduces mesangial hypertrophy and kidney tubular fibrosis via MAPK signalling

2017 ◽  
Vol 131 (5) ◽  
pp. 411-423 ◽  
Author(s):  
Bo Wang ◽  
Kevin Yao ◽  
Andrea F. Wise ◽  
Ricky Lau ◽  
Hsin-Hui Shen ◽  
...  
Keyword(s):  
Type Iv Collagen ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Mesangial Cell ◽  
Quantitative Polymerase Chain Reaction ◽  
Locked Nucleic Acid ◽  
Type I ◽  
Protective Function ◽  
Type Iv ◽  
Tgf Β1

The regulatory role of a novel miRNA, miR-378, was determined in the development of fibrosis through repression of the MAPK1 pathway, miR-378 and fibrotic gene expression was examined in streptozotocin (STZ)-induced diabetic mice at 18 weeks or in unilateral ureteral obstruction (UUO) mice at 7 days. miR-378 transfection of proximal tubular epithelial cells, NRK52E and mesangial cells was assessed with/without endogenous miR-378 knockdown using the locked nucleic acid (LNA) inhibitor. NRK52E cells were co-transfected with the mothers against decapentaplegic homolog 3 (SMAD3) CAGA reporter and miR-378 in the presence of transforming growth factor-β (TGF-β1) was assessed. Quantitative polymerase chain reaction (qPCR) showed a significant reduction in miR-378 (P<0.05) corresponding with up-regulated type I collagen, type IV collagen and α-smooth muscle actin (SMA) in kidneys of STZ or UUO mice, compared with controls. TGF-β1 significantly increased mRNA expression of type I collagen (P<0.05), type IV collagen (P<0.05) and α-SMA (P<0.05) in NRK52E cells, which was significantly reduced (P<0.05) following miR-378 transfection and reversed following addition of the LNA inhibitor of endogenous miR-378. Overexpression of miR-378 inhibited mesangial cell expansion and proliferation in response to TGF-β1, with LNA–miR-378 transfection reversing this protective effect, associated with cell morphological alterations. The protective function of MAPK1 on miR-378 was shown in kidney cells treated with the MAPK1 inhibitor, selumetinib, which inhibited mesangial cell hypertrophy in response to TGF-β1. Taken together, these results suggest that miR-378 acts via regulation of the MAPK1 pathway. These studies demonstrate the protective function of MAPK1, regulated by miR-378, in the induction of kidney cell fibrosis and mesangial hypertrophy.

scholarly journals Structure of the Human Type IV Collagen Gene COL4A3 and Mutations in Autosomal Alport Syndrome

2001 ◽  
Vol 12 (1) ◽  
pp. 97-106
Author(s):  
LAURENCE HEIDET ◽  
CHRISTELLE ARRONDEL ◽  
LIONEL FORESTIER ◽  
LOLA COHEN-SOLAL ◽  
GERALDINE MOLLET ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Autosomal Recessive ◽  
Type Iv Collagen ◽  
Collagen Gene ◽  
Missense Mutations ◽  
Autosomal Recessive Form ◽  
Type Iv ◽  
Recessive Form ◽  
Genes Encoding ◽  
Intron Structure

Abstract. Mutations in either the COL4A3 or the COL4A4 genes, encoding the α3 and α4 chains of type IV collagen, are responsible for the autosomal-recessive form of Alport syndrome, a progressive hematuric nephropathy characterized by glomerular basement membrane abnormalities. Reported here are the complete COL4A3 exon-intron structure and a comprehensive screen for mutations of the 52 COL4A3 exons in 41 unrelated patients diagnosed as having autosomal Alport syndrome. This resulted in the identification of 21 mutations that are expected to be causative. Furthermore, it is shown that heterozygous COL4A3 missense mutations, when symptomatic, can be associated with a broad range of phenotypes, from familial benign hematuria to the complete features of Alport syndrome nephropathy.

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