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Response gene to complement 32 in renal fibrosis
Author(s) -
Chen ShiYou,
Li Zuguo,
Escano Crisanto S,
Asico Laureano,
Jose Pedro A
Publication year - 2010
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.24.1_supplement.793.10
Subject(s) - myofibroblast , kidney , pathology , fibrosis , fibronectin , gene knockdown , biology , medicine , microbiology and biotechnology , endocrinology , cell culture , extracellular matrix , genetics
Previous studies have shown that response gene to complement 32 (RGC‐32) mediates TGF‐β‐induced epithelial‐mesenchymal transition of human renal proximal tubule cells. The current study is to determine if RGC‐32 is involved in the pathogenesis of renal fibrosis using unilateral ureteral obstruction (UUO) mouse model. RGC‐32 is normally expressed only in blood vessels of mouse kidney. After 5 days of UUO, RGC‐32 is strongly expressed in kidney interstitial cells and weakly in tubular cells, suggesting that UUO induces RGC‐32 expression. α‐SMA staining is limited to the interstitial cells at this early stage of renal fibrosis, suggesting that α‐SMA‐expressing myofibroblasts are derived from interstitial cells. Blockade of RGC‐32 by perfusion of RGC‐32 shRNA into kidney with UUO inhibited the expression of α‐SMA in the interstitium. In vitro studies showed that TGF‐β induced fibroblast activation while inducing RGC‐32 expression. Knockdown of RGC‐32 in fibroblasts blocked the expression of myofibroblast markers α‐SMA, collagen and fibronectin. Our data demonstrate that RGC‐32 plays an important role in the onset of renal fibrosis. (Funding source: NIH R01HL093429)