Angiotensin mediates renal fibrosis in the nephropathy of glycogen storage disease type la

作者：Yiu W H; Pan C J; Ruef R A; Peng W T; Starost M F; Mansfield B C; Chou J Y^*

来源：Kidney International, 2008, 73(6): 716-723.

DOI：10.1038/sj.ki.5002718

• angiotensin
• connective tissue growth factor
• glycogen storage disease type la
• renal fibrosis
• transforming growth factor-beta 1

Patients with glycogen storage disease type la (GSD-la) develop renal disease of unknown etiology despite intensive dietary therapies. This renal disease shares many clinical and pathological similarities to diabetic nephropathy. We studied the expression of angiotensinogen, angiotensin type 1 receptor, transforming growth factor-beta 1, and connective tissue growth factor in mice with GSD-la and found them to be elevated compared to controls. While increased renal expression of angiotensinogen was evident in 2-week-old mice with GSD-la, the renal expression of transforming growth factor-beta and connective tissue growth factor did not increase for another week; consistent with upregulation of these factors by angiotensin II. The expression of fibronectin and collagens I, III, and IV was also elevated in the kidneys of mice with GSD-la, compared to controls. Renal fibrosis was characterized by a marked increase in the synthesis and deposition of extracellular matrix proteins in the renal cortex and histological abnormalities including tubular basement membrane thickening, tubular atrophy, tubular dilation, and multifocal interstitial fibrosis. Our results suggest that activation of the angiotensin system has an important role in the pathophysiology of renal disease in patients with GSD-la.

• 出版日期2008-3
• 单位NIH