BACKGROUND: In our rat model for anti-GBM GN, severe fibrosis follows glomerular inflammation. A potential role of extracellular matrix protein osteopontin (OPN) in glomerular fibrosis was investigated. METHODS: Neutralizing OPN antiserum or control normal serum was injected into the experimental rats at late inflammatory/early fibrotic stage. Glomerular inflammation and fibrosis were determined. RESULTS: OPN antiserum treatment had little effect on glomerular inflammation. However, the antiserum treatment resulted in a significant reduction in number of fibrotic glomeruli (50% of the controls). Histology observation showed that fibrotic tissue in glomeruli of the antiserum treated rats was mild and poorly developed. OPN antiserum treatment resulted in downregulated glomerular expression of collagen 1α1; collagen deposition in the antiserum treated rats reduced to <30% of that for normal serum controls. CONCLUSION: Neutralization of OPN inhibited progression of fibrosis in vivo when given at early fibrotic stage. Thus, OPN may be a therapeutic target for glomerular fibrosis.
BACKGROUND: In our rat model for anti-GBM GN, severe fibrosis follows glomerular inflammation. A potential role of extracellular matrix protein osteopontin (OPN) in glomerular fibrosis was investigated. METHODS: Neutralizing OPN antiserum or control normal serum was injected into the experimental rats at late inflammatory/early fibrotic stage. Glomerular inflammation and fibrosis were determined. RESULTS:OPN antiserum treatment had little effect on glomerular inflammation. However, the antiserum treatment resulted in a significant reduction in number of fibrotic glomeruli (50% of the controls). Histology observation showed that fibrotic tissue in glomeruli of the antiserum treated rats was mild and poorly developed. OPN antiserum treatment resulted in downregulated glomerular expression of collagen 1α1; collagen deposition in the antiserum treated rats reduced to <30% of that for normal serum controls. CONCLUSION: Neutralization of OPN inhibited progression of fibrosis in vivo when given at early fibrotic stage. Thus, OPN may be a therapeutic target for glomerular fibrosis.
Authors: D Chabas; S E Baranzini; D Mitchell; C C Bernard; S R Rittling; D T Denhardt; R A Sobel; C Lock; M Karpuj; R Pedotti; R Heller; J R Oksenberg; L Steinman Journal: Science Date: 2001-11-23 Impact factor: 47.728
Authors: John Michael Bonvini; Ursula Schatzmann; Beatrice Beck-Schimmer; Li Kang Sun; Susan R Rittling; David T Denhardt; Michel LE Hir; Rudolf P Wüthrich Journal: J Am Soc Nephrol Date: 2000-09 Impact factor: 10.121
Authors: Jessica Trostel; Luan D Truong; Carlos Roncal-Jimenez; Makoto Miyazaki; Shinobu Miyazaki-Anzai; Masanari Kuwabara; Rachel McMahan; Ana Andres-Hernando; Yuka Sato; Thomas Jensen; Miguel A Lanaspa; Richard J Johnson; Gabriela E Garcia Journal: Am J Physiol Renal Physiol Date: 2018-05-02