TY - JOUR
T1 - Osteopontin modulates angiotensin II-induced inflammation, oxidative stress, and fibrosis of the kidney
AU - Wolak, Talya
AU - Kim, Hyunju
AU - Ren, Yuelan
AU - Kim, Jason
AU - Vaziri, Nosratola D.
AU - Nicholas, Susanne B.
N1 - Funding Information:
TW received funding from American Physicians Fellowship for Medicine in Israel. This work was supported by the Wilson Foundation, P01HD048721 and NIH/NHLBI RO1 HL071792-04. Some of these results were presented in poster form at the American Society of Nephrology, San Francisco, CA 2007 and Experimental Biology, San Diego, CA 2008. We thank Dr Willa A. Hsueh for her support.
PY - 2009/1/1
Y1 - 2009/1/1
N2 - Osteopontin, a secreted glycoprotein has been implicated in several renal pathological conditions such as those due to ureteral obstruction, ischemia, and cyclosporine toxicity. We studied its possible role in angiotensin II-mediated renal injury by infusing wild-type and osteopontin knockout mice with angiotensin II and found that it raised blood pressure and increased urinary albumin/creatinine ratios in both strains of mice. However, while wild-type mice responded to the infusion by macrophage infiltration and increased expression of α-smooth muscle actin, fibronectin, and transforming growth factor-Β; the osteopontin knockout mice developed none of these. Further, the knockout mice had increased expression of monocyte chemoattractant protein-1; NADPH oxidase subunits such as NOX2, gp47phox, and NOX4; and plasminogen activator inhibitor-1 compared to the wild type animals. Proximal tubule epithelial cells in culture treated with recombinant osteopontin and angiotensin II had increased α-smooth muscle actin and transforming growth factor-Β expression. The effect of angiotensin II was blocked by an antibody to osteopontin. In addition, osteopontin attenuated angiotensin II-induced plasminogen activator inhibitor-1 expression. These studies show that osteopontin is a promoter and an inhibitor of inflammation, oxidative stress, and fibrosis that is capable of modulating angiotensin II-induced renal damage.
AB - Osteopontin, a secreted glycoprotein has been implicated in several renal pathological conditions such as those due to ureteral obstruction, ischemia, and cyclosporine toxicity. We studied its possible role in angiotensin II-mediated renal injury by infusing wild-type and osteopontin knockout mice with angiotensin II and found that it raised blood pressure and increased urinary albumin/creatinine ratios in both strains of mice. However, while wild-type mice responded to the infusion by macrophage infiltration and increased expression of α-smooth muscle actin, fibronectin, and transforming growth factor-Β; the osteopontin knockout mice developed none of these. Further, the knockout mice had increased expression of monocyte chemoattractant protein-1; NADPH oxidase subunits such as NOX2, gp47phox, and NOX4; and plasminogen activator inhibitor-1 compared to the wild type animals. Proximal tubule epithelial cells in culture treated with recombinant osteopontin and angiotensin II had increased α-smooth muscle actin and transforming growth factor-Β expression. The effect of angiotensin II was blocked by an antibody to osteopontin. In addition, osteopontin attenuated angiotensin II-induced plasminogen activator inhibitor-1 expression. These studies show that osteopontin is a promoter and an inhibitor of inflammation, oxidative stress, and fibrosis that is capable of modulating angiotensin II-induced renal damage.
KW - Angiotensin II
KW - Fibrosis
KW - Inflammation
KW - Osteopontin
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=67449116323&partnerID=8YFLogxK
U2 - 10.1038/ki.2009.90
DO - 10.1038/ki.2009.90
M3 - Article
C2 - 19357716
AN - SCOPUS:67449116323
SN - 0085-2538
VL - 76
SP - 32
EP - 43
JO - Kidney International
JF - Kidney International
IS - 1
ER -