title: Cordycepin inhibits renal interstitial myofibroblast activation probably by inducing hepatocyte growth factor expression.
abstract: Renal interstitial fibrosis is the common end point of progressive renal diseases leading to the deterioration and eventual loss of renal function. This study investigated the effect and potential mechanism of cordycepin on activation of renal interstitial fibroblast cells. The time and dose-responses of cordycepin in rat renal interstitial fibroblast (NRK-49F) cells were analyzed. The proliferation of NRK-49F and the expression of α-smooth muscle actin (α-SMA) and fibronectin (FN) were examined. The expression and translocation of Smad proteins also were measured by western blot and indirect immunofluorescence staining. The mRNA level of hepatocyte growth factor (HGF) and the expression of HGF receptor c-Met and its phosphorylation (p-Met) were also detected. Cordycepin suppressed the proliferation of NRK-49F and the expression of α-SMA and FN induced by transforming growth factor-β1 (TGF-β1). The pretreatment of cordycepin markedly attenuated the nuclear translocation and accumulation of activated Smad2/3 in NRK-49F cells. Furthermore, cordycepin not only increased HGF expression, but also induced HGF secretion, as well as HGF receptor phosphorylation in NRK-49F cells. Cordycepin possesses renoprotective activity through suppression myofibroblast activation. This action is mediated, at least in part, by blocking nuclear translocation and accumulation of activated Smad2/3 protein and up-regulating anti-fibrotic HGF expression and secretion and HGF receptor activation.
authors: First Clinical Medical College of Nanjing Medical University, Nanjing 210029, PR China. listanding@hotmail.com
authors: Li
authors: L
authors: Li
authors: Dongyuan
authors: D
authors: He
authors: Junwei
authors: J
authors: Yang
authors: Xiaoyun
authors: X
authors: Wang
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003839:Deoxyadenosines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D000199:Actins; D003839:Deoxyadenosines; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat; C058120:cordycepin