scholarly journals Transforming growth factor beta mediates the angiotensin-II-induced stimulation of collagen type IV synthesis in cultured murine proximal tubular cells

1996 ◽  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Collagen Type Iv ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Type Iv ◽  
Proximal Tubular ◽  
Growth Factor Beta ◽  
Stimulation Of

Transforming growth factor-beta modulation of the alpha 1(IV) collagen gene in murine proximal tubular cells

1996 ◽  
Vol 271 (1) ◽  
pp. F120-F125 ◽  
Author(s):  
G. S. Kuncio ◽  
R. Alvarez ◽  
S. Li ◽  
P. D. Killen ◽  
E. G. Neilson
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Bidirectional Promoter ◽  
Collagen Gene ◽  
Tgf Beta ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Type Iv ◽  
Proximal Tubular ◽  
Growth Factor Beta

We have examined the expression of the alpha 1(IV) collagen gene in murine proximal tubular cells (MCT) to better understand how it is regulated in parenchymal cells. Transcriptional activity was examined using luciferase reporters driven by the alpha 1(IV) promoter and varying lengths of 5'-flanking sequences. The minimal bidirectional promoter showed low intrinsic activity in MCT cells, but addition of upstream sequences increased luciferase expression. Maximal activity resided within the first 1,200 bp upstream. A minigene construct was generated by placing a portion of the alpha 1(IV) first intron downstream from the promoter region. The intronic sequences significantly decreased activity of the promoter in MCT cells and 3T3 fibroblasts but greatly enhanced expression in murine parietal yolk sac (PYS) endodermal cells. Addition of transforming growth factor-beta (TGF-beta) to MCT cultures elevated the levels of secreted type IV collagen. Treatment of either transiently or stably transfected MCT cells with TGF-beta produced an increase in the levels of expression of all of the reporters tested. These data support the hypothesis that cell-specific regulation of alpha 1(IV) collagen is dependent upon downstream sequences, which act to decrease the expression of type IV collagen in tubular epithelium. The activity of the alpha 1(IV) collagen gene in proximal tubular cells is increased by TGF-beta, which acts on the domain(s) embedded within the intergenic bidirectional promoter.

scholarly journals Essential Role(s) of the Intrarenal Renin-Angiotensin System in Transforming Growth Factor–β1 Gene Expression and Induction of Hypertrophy of Rat Kidney Proximal Tubular Cells in High Glucose

2002 ◽  
Vol 13 (2) ◽  
pp. 302-312
Author(s):  
Shao-Ling Zhang ◽  
Catherine To ◽  
Xing Chen ◽  
Janos G. Filep ◽  
Shiow-Shih Tang ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Type Iv ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular ◽  
Tgf Β1

ABSTRACT. These studies investigated the question of whether the intrarenal renin-angiotensin system (RAS) is essential for transforming growth factor–β1 (TGF-β1) gene expression and induction of hypertrophy of renal proximal tubular cells in high glucose in vitro. Antisense and sense angiotensinogen (ANG) cDNAs were stably transfected into rat immortalized renal proximal tubular cells (IRPTC). ANG secretion from rat IRPTC was quantified by a specific RIA for rat ANG. Cellular ANG, TGF-β1, and collagen α1 (type IV) mRNA levels were determined by Northern blot analysis or by reverse transcriptase–PCR assay. Hypertrophy of IRPTC was analyzed by Western blotting of cellular p27Kip1 protein, flow cytometry, and cellular protein assay. The results showed that stable transfer of antisense ANG cDNA into IRPTC suppressed the basal TGF-β1 and collagen α1 (type IV) mRNA expression and blocked the stimulatory effect of high glucose (i.e., 25 mM) on TGF-β1 and collagen α1 (type IV) mRNA expression and induction of IRPTC hypertrophy. In contrast, stable transfer of sense ANG cDNA into IRPTC had no significant effect on these parameters. These data demonstrate that local intrarenal RAS activation is essential for TGF-β1 gene expression and induction of hypertrophy of renal proximal tubular cells in high glucose.

Sign in / Sign up

Export Citation Format

Share Document