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SPARC deficiency ameliorates renal damage resulting from angiotensin II and a high salt diet
Author(s) -
Socha Matthew John,
Manhiani Marlina,
Motamed Kouros,
Imig John D,
Inscho Edward W
Publication year - 2009
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.23.1_supplement.604.1
Subject(s) - medicine , endocrinology , angiotensin ii , renal function , albuminuria , urinary system , matricellular protein , kidney , oxidative stress , hypertensive nephropathy , blood pressure , chemistry , diabetic nephropathy , extracellular matrix , biochemistry
Markedly elevated levels of matricellular protein SPARC (Secreted Protein Acidic and Rich in Cysteine, SP ) have been found in serum of patients with fibrotic renal injury and in glomeruli of hypertensive injury. Our previous data indicate that SPARC deficiency resulted in decreased renal fibrosis, oxidative stress, and inflammation following Angiotensin II (Ang II)‐induced hypertension, with no improvement in renal function. We hypothesized that SPARC deficiency would attenuate the detrimental renal effects and protect kidney function in Ang II‐induced hypertension combined with a high salt diet. Following a 2‐week Ang II infusion combined with a high salt diet (4% w/v), and independent of blood pressure differences ( SP +/+ 163 ± 4, SP −/− 162 ± 3 mmHg), SP −/− mice showed significant attenuations in albuminuria (urinary albumin decreased 70.7%), renal matrix deposition (urinary levels of active TGF‐β1 decreased 58.9%), reactive oxygen species formation (urinary 8‐isoprostane decreased 60.9%), and renal inflammatory responses (MCP‐1 and IL‐1β levels decreased 36.8% and 59.8%, respectively), relative to SP +/+ controls. We conclude that in a severe model of hypertension, SPARC deficiency protects against renal hypertensive damage at the cellular and functional levels. This work is supported in part by National Institute of Health grants K01‐CA089689 (to K.M.) and HL59699 (to J.D.I.).