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 d...

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Main Authors: Li Li, Dongyuan He, Junwei Yang, Xiaoyun Wang
Format: Article
Language:English
Published: Elsevier 2011-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319306152
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author Li Li
Dongyuan He
Junwei Yang
Xiaoyun Wang
author_facet Li Li
Dongyuan He
Junwei Yang
Xiaoyun Wang
author_sort Li Li
collection DOAJ
description 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 upregulating anti-fibrotic HGF expression and secretion and HGF receptor activation. Keywords:: cordycepin, hepatocyte growth factor, transforming growth factor-β1, myofibroblast, renal fibrosis
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spelling doaj.art-5b5222a2a3494962a5aa29a2103fb77b2022-12-22T00:43:04ZengElsevierJournal of Pharmacological Sciences1347-86132011-01-011174286294Cordycepin Inhibits Renal Interstitial Myofibroblast Activation Probably by Inducing Hepatocyte Growth Factor ExpressionLi Li0Dongyuan He1Junwei Yang2Xiaoyun Wang3First Clinical Medical College of Nanjing Medical University, Nanjing 210029, P.R. China; Present address: Department of Nephrology, Yangzhou No.1 People’s Hospital, Yangzhou 225012, P.R. China; Corresponding authors. *alistanding@hotmail.com, *bxywang1941@126.comFirst Clinical Medical College of Nanjing Medical University, Nanjing 210029, P.R. China; Present address: Department of Nephrology, Zhejiang Hospital, Hangzhou 310013, P.R. ChinaDepartment of Nephrology, 2nd Affiliated Hospital of Nanjing Medical University, Nanjing 210011, P.R. ChinaFirst Clinical Medical College of Nanjing Medical University, Nanjing 210029, P.R. China; Corresponding authors. *alistanding@hotmail.com, *bxywang1941@126.comAbstract.: 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 upregulating anti-fibrotic HGF expression and secretion and HGF receptor activation. Keywords:: cordycepin, hepatocyte growth factor, transforming growth factor-β1, myofibroblast, renal fibrosishttp://www.sciencedirect.com/science/article/pii/S1347861319306152
spellingShingle Li Li
Dongyuan He
Junwei Yang
Xiaoyun Wang
Cordycepin Inhibits Renal Interstitial Myofibroblast Activation Probably by Inducing Hepatocyte Growth Factor Expression
Journal of Pharmacological Sciences
title Cordycepin Inhibits Renal Interstitial Myofibroblast Activation Probably by Inducing Hepatocyte Growth Factor Expression
title_full Cordycepin Inhibits Renal Interstitial Myofibroblast Activation Probably by Inducing Hepatocyte Growth Factor Expression
title_fullStr Cordycepin Inhibits Renal Interstitial Myofibroblast Activation Probably by Inducing Hepatocyte Growth Factor Expression
title_full_unstemmed Cordycepin Inhibits Renal Interstitial Myofibroblast Activation Probably by Inducing Hepatocyte Growth Factor Expression
title_short Cordycepin Inhibits Renal Interstitial Myofibroblast Activation Probably by Inducing Hepatocyte Growth Factor Expression
title_sort cordycepin inhibits renal interstitial myofibroblast activation probably by inducing hepatocyte growth factor expression
url http://www.sciencedirect.com/science/article/pii/S1347861319306152
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AT dongyuanhe cordycepininhibitsrenalinterstitialmyofibroblastactivationprobablybyinducinghepatocytegrowthfactorexpression
AT junweiyang cordycepininhibitsrenalinterstitialmyofibroblastactivationprobablybyinducinghepatocytegrowthfactorexpression
AT xiaoyunwang cordycepininhibitsrenalinterstitialmyofibroblastactivationprobablybyinducinghepatocytegrowthfactorexpression