Elevated transcriptional co-activator p102 mediates angiotensin II type 1 receptor up-regulation and extracellular matrix overproduction in the high glucose-treated rat glomerular mesangial cells and isolated glomeruli

2013 ◽  
Vol 702 (1-3) ◽  
pp. 208-217 ◽  
Author(s):  
Zhen Wang ◽  
Jun Ni ◽  
Decui Shao ◽  
Jia Liu ◽  
Yang Shen ◽  
...  
1991 ◽  
Vol 260 (2) ◽  
pp. F185-F191 ◽  
Author(s):  
S. H. Ayo ◽  
R. A. Radnik ◽  
W. F. Glass ◽  
J. A. Garoni ◽  
E. R. Rampt ◽  
...  

Nodular expansion of glomerular mesangium with increased amounts of extracellular matrix (ECM) material is pathognomic of diabetic nephropathy. The precise mechanisms involved in this accumulation are unknown. Recently, we reported using a solid-phase enzyme-linked immunosorbent assay (ELISA) technique that glomerular mesangial cells, the principal cell type residing in glomerular mesangium, accumulate 50–60% more fibronectin (FN), laminin (LM), and type IV collagen (T-IV) when cultured in medium containing high glucose (30 mM) (S. H. Ayo, R. A. Rodnik, J. Garoni, W. F. Glass II, and J. I. Kreiberg. Am. J. Pathol. 136: 1339-1348, 1990). ECM assembly is controlled by its rate of synthesis and degradation, as well as its binding and rate of incorporation into the ECM. To elucidate the mechanisms involved, pulse-chase experiments were designed to estimate ECM protein synthesis from the incorporation of Trans-35S [( 35S]methionine, [35S]cysteine) into immunoprecipitated FN, LM, and T-IV. mRNA levels were examined, and degradation rates were estimated from the disappearance of radioactivity from matrix proteins in mesangial cells previously incubated with Trans-35S. One week of growth in 30 mM glucose resulted in approximately 40–50% increase in the synthesis of all three matrix proteins compared with 10 mM glucose-grown cells. This was accompanied by a significant increase in the transcripts for all three matrix proteins (approximately twofold). The specific activity of the radiolabel in trichloroacetic acid-precipitable cell protein showed no difference between cells grown in 10 or 30 mM glucose, indicating that total protein synthesis was unchanged. After 1 wk, the rate of FN, LM, and T-IV collagen degradation was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)


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