title: Curcumin ameliorates renal fibrosis by inhibiting local fibroblast proliferation and extracellular matrix deposition.
abstract: Renal fibrosis is mainly characterized by activation and proliferation of interstitial fibroblasts and by excessive synthesis and accumulation of extracellular matrix (ECM) components, including fibronectin (FN) and collagen. This study investigated the effects of curcumin on proliferation of renal interstitial fibroblasts and their underlying mechanisms in vivo and in vitro. ECM components were visualized by Sirius red and immunohistochemistry staining and quantified by western blot analysis in mice with unilateral ureteral obstruction (UUO). Duplex staining for proliferating cell nuclear antigen and α-smooth muscle actin (α-SMA), as well as MTT and flow cytometry assays, were performed to measure fibroblast proliferation. Protein expression of phosphorylated Smad2/3 (p-Smad2/3) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were assessed by western blotting. Curcumin treatment decreased the accumulation of type I collagen and FN in the kidney of animals with UUO. Activation of rat renal interstitial fibroblasts (NRK-49F) was induced by TGF-β1. Curcumin treatment inhibited fibroblast proliferation and the cell cycle was arrested in the G1 phase. Curcumin treatment upregulated the expression of PPAR-γ and downregulated the expression of p-Smad2/3. These results suggest that curcumin treatment ameliorates renal fibrosis by reducing fibroblast proliferation and ECM accumulation mediated by PPAR-γ and Smad-dependent TGF-β1 signaling.
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University, China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Changgeng
authors.initials: C
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D003864:Depression, Chemical; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein / Q000235:genetics / Q000502:physiology; D051900:Smad3 Protein / Q000235:genetics / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000502:physiology
chemical_list: D005353:Fibronectins; D047495:PPAR gamma; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D003094:Collagen; D003474:Curcumin