Faculty Collaboration Database

Secreted protein acidic and rich in cysteine deficiency ameliorates renal inflammation and fibrosis in angiotensin hypertension. Am J Pathol 2007 Oct;171(4):1104-12

Date

08/25/2007

Pubmed ID

17717147

Pubmed Central ID

PMC1988862

DOI

10.2353/ajpath.2007.061273

Scopus ID

2-s2.0-35348852466 (requires institutional sign-in at Scopus site)   56 Citations

Abstract

The matricellular protein secreted protein acidic and rich in cysteine (SPARC) modulates cell adhesion, proliferation, matrix deposition, and tissue remodeling. SPARC has been shown to regulate the expression of collagen type I and transforming growth factor-beta1 in mesangial cells and to be highly expressed during tubulointerstitial fibrosis in rat angiotensin (ANG) II infusion models. We hypothesized that SPARC is a downstream effector of ANG II and that loss of host SPARC function provides a protective effect on renal damage and fibrosis associated with ANG II hypertension. Our results revealed that cultured primary mesangial cells displayed a concentration-dependent increase in SPARC expression in response to ANG II. After a 14-day chronic infusion of ANG II, hypertensive SPARC-null mice exhibited significantly attenuated levels of urinary and renal indicators of oxidative stress and inflammation and decreased renal perivascular and tubulointerstitial fibrosis relative to wild-type hypertensive controls. Moreover, the observed renal protective changes in SPARC-null mice were found to be independent of blood pressure. These results identify SPARC as an effector of ANG II signaling and suggest an important role for SPARC in mediating ANG II-induced oxidative stress, inflammation, and fibrosis.

Author List

Socha MJ, Manhiani M, Said N, Imig JD, Motamed K

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Blood Pressure
Disease Progression
Fibrosis
Glomerular Mesangium
Humans
Hypertension, Renal
Male
Matrix Metalloproteinase 2
Mice
Mice, Mutant Strains
Osteonectin
RNA, Messenger
Rats
Reactive Oxygen Species
Signal Transduction
Transforming Growth Factor beta1