title: Cordyceps sinensis polysaccharide CPS-2 protects human mesangial cells from PDGF-BB-induced proliferation through the PDGF/ERK and TGF-β1/Smad pathways.
abstract: CPS-2, a Cordyceps sinensis polysaccharide, has been demonstrated to have significant therapeutic activity against chronic renal failure. However, little is known about the underlying molecular mechanism. In this study, we found that CPS-2 could inhibit PDGF-BB-induced human mesangial cells (HMCs) proliferation in a dose-dependent manner. In addition, CPS-2 notably suppressed the expression of α-SMA, PDGF receptor-beta (PDGFRβ), TGF-β1, and Smad 3 in PDGF-BB-treated HMCs. Furthermore, PDGF-BB-stimulated ERK activation was significantly inhibited by CPS-2, and this inhibitory effect was synergistically potentiated by U0126. CPS-2 could prevent the PDGFRβ promoter activity induced by PDGF-BB, and return expression of PDGFRβ, TGF-β1, and TGFβRI to normal levels while cells were under PDGFRβ and ERK silencing conditions and transfected with DN-ERK. Taken together, these findings demonstrated that CPS-2 reduces PDGF-BB-induced cell proliferation through the PDGF/ERK and TGF-β1/Smad pathways, and it may have bi-directional regulatory effects on the PDGF/ERK cellular signaling pathway.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China; School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, Jiangsu, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, Jiangsu, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, Jiangsu, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: First Clinical Medical College, Nanjing University of Traditional Chinese Medicine, Nanjing Traditional Chinese Medicine Hospital, Nanjing 210010, Jiangsu, People's Republic of China.
authors.forename: Huixing
authors.initials: H
authors.lastname: Jiang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, Jiangsu, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Luo
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, Jiangsu, People's Republic of China. Electronic address: minwang@cpu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China; School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, Jiangsu, People's Republic of China. Electronic address: yinhongping63@hotmail.com.
authors.forename: Hongping
authors.initials: H
authors.lastname: Yin
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000077214:Becaplermin; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D032661:Cordyceps / Q000737:chemistry*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics* / Q000378:metabolism; D062610:Fungal Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D050527:Mesangial Cells; D009570:Nitriles / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D051900:Smad3 Protein / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D002070:Butadienes; D004791:Enzyme Inhibitors; D062610:Fungal Polysaccharides; D009570:Nitriles; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C113580:U 0126; D000077214:Becaplermin; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Cordyceps sinensis; ERK; Mesangial cells; PDGF-BB; Polysaccharide; TGF-β1