title: Angiotensin mediates renal fibrosis in the nephropathy of glycogen storage disease type Ia.
abstract: Patients with glycogen storage disease type Ia (GSD-Ia) 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-beta1, and connective tissue growth factor in mice with GSD-Ia and found them to be elevated compared to controls. While increased renal expression of angiotensinogen was evident in 2-week-old mice with GSD-Ia, 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-Ia, 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-Ia.
authors: Section on Cellular Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: W H
authors: WH
authors: Yiu
authors: C-J
authors: CJ
authors: Pan
authors: R A
authors: RA
authors: Ruef
authors: W-T
authors: WT
authors: Peng
authors: M F
authors: MF
authors: Starost
authors: B C
authors: BC
authors: Mansfield
authors: J Y
authors: JY
authors: Chou
mesh_terms: D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000809:Angiotensins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D055513:Connective Tissue Growth Factor; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D005952:Glucose-6-Phosphatase / Q000235:genetics; D005953:Glycogen Storage Disease Type I / Q000150:complications*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000809:Angiotensins; C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D044140:Receptor, Angiotensin, Type 1; D053773:Transforming Growth Factor beta1; D000808:Angiotensinogen; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D005952:Glucose-6-Phosphatase