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Osteopontin Deficiency Attenuates Tubulointerstitial Injury in Angiotensin II‐Infused Mice.
Author(s) -
Wolak Talya,
Ren Yuelan,
Kim Jason,
Collins Alan,
Hsueh Willa,
Nicholas Susanne
Publication year - 2008
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.22.1_supplement.969.32
Subject(s) - osteopontin , endocrinology , chemistry , medicine , cd68 , kidney , angiotensin ii , inflammation , immunohistochemistry , receptor
Our aim was to examine the role of Osteopontin (OPN) in tubulointerstial injury induced by AngiotensinII (AngII). We infused OPN‐null (OPN −/− ; n=24) and wild type (OPN +/+ ; n=22) mice with AngII (2.5μg/kg/min) or vehicle. Blood pressure (BP) and 24‐hour urine albumin‐to‐creatinine ratio (ACR) were measured. After 28 days, kidneys were sectioned for immunhistochemistry (IHC) and immunofluorescence (IF) to detect macrophage with MOMA‐2 and CD68 and epithelial cell transformation (EMT) with α‐smooth muscle actin (α‐SMA). Kidney cortex mRNA was used for MCP‐1.Kidney tubular epithelial (LLC‐PK1) cells were incubated with recombinant OPN (10nM) for 4, 8, 16 and 24 h (n=4) and then analyzed for TGFβ‐1 and α‐SMA protein. BP and ACR increased equally in AngII‐infused OPN +/+ and AngII‐infused OPN −/− . There was significantly lower tubulointerstial macrophage infiltration (by MOMA‐2; 1.6±0.2 vs. 2.8±0.2, p<0.01 and CD68; 0.58±0.15 vs. 2.18±0.25, p<0.01) and α‐SMA (4.9±0.5 vs. 9.1±0.6%, p<0.01), in the AngII‐infused OPN −/− vs. AngII‐infused OPN +/+ . MCP‐1 mRNA was 4.5 fold higher in AngII‐infused OPN −/− vs. AngII‐infused OPN +/+ mice (p<0.05). Recombinant OPN increased α‐SMA and TGFβ‐1 expression in LLC‐PK1 after 8 and 24 hours of culture, respectively. The results of our study indicate that OPN recruits macrophages and enhances the expression of EMT markers. However, inflammation is modulated by down regulation of MCP‐1.