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SPARC deficiency ameliorates renal fibrosis and inflammation in Angiotensin hypertension
Author(s) -
Socha Matthew John,
Manhiani Marlina,
Said Neveen,
Imig John,
Motamed Kouros
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a591-d
Subject(s) - endocrinology , angiotensin ii , medicine , matricellular protein , fibrosis , inflammation , kidney , blood pressure , cyr61 , hypertensive nephropathy , renin–angiotensin system , renal injury , extracellular matrix , chemistry , ctgf , receptor , diabetic nephropathy , growth factor , biochemistry
Markedly elevated levels of matricellular protein SPARC (Secreted Protein Acidic and Rich in Cysteine) have been found in serum of patients with fibrotic renal injury and in glomeruli of hypertensive injury models including Angiotensin (Ang) II infusion. Our supportive data indicates that Ang II induces a dose‐dependent increase in SPARC expression of cultured human mesangial cells. We therefore hypothesized that SPARC deficiency alleviates the detrimental renal effects of Ang II‐induced hypertension. Following a 2‐week Ang II infusion, and independent of any hemodynamic changes, SPARC‐null mice showed significant attenuations in renal perivascular and tubulointerstitial matrix deposition (urinary levels of active TGF‐β1 decreased 43.3% and MMP‐2 decreased by >10‐fold), reactive oxygen species formation (8‐isoprostane decreased by 49.8%), and renal inflammatory responses (MCP‐1 and IL‐1β levels decreased by 59.5% and 78.3%, respectively), relative to wild‐type hypertensive controls. We conclude that targeted knockdown of SPARC could prove to be a potential therapeutic strategy for amelioration of hypertensive renal injury independent of effects on blood pressure. This work is supported in part by National Institute of Health grants K01‐CA089689 (to K.M.) and HL59699 (to J.D.I.).