title: Bufalin inhibits platelet-derived growth factor-BB-induced mesangial cell proliferation through mediating cell cycle progression.
abstract: Bufalin, a traditional Chinese medicine, has been reported as a protective factor in many tumors. We therefore investigated the effect of bufalin on platelet-derived growth factor (PDGF)-BB-induced proliferation of cultured rat mesangial cells. The effect of bufalin on cell proliferation and its underlying mechanisms were investigated in cultured rat mesangial cells (MCs) by the methylthiazoletetrazolium (MTT) assay, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and cyclin-dependent kinases (CDK)2 and CDK4 kinase assays. Bufalin inhibited 20 ng/ml PDGF-BB-induced MC proliferation in a dose-dependent manner. Similar results were observed in different concentrations of bufalin, which blocked PDGF-BB-induced progression through G0/G1 to S phase of the cell cycle. Furthermore, bufalin not only inhibited upregulation of cyclin D1 and CDK4, but also downregulation of p21 in both mRNA and protein levels. Although bufalin did not affect p27 and CDK2 mRNA expression, it reversed downregulation of p27 and upregulation of CDK2 in protein level. Activity of CDK2 and CDK4 was also inhibited by bufalin. However, both bufalin and PDGF-BB did not affect cyclin E mRNA or protein expression. These results suggest that bufalin could inhibit MC proliferation by modulating cell cycle progress, indicating that bufalin could be a potential therapeutic agent for the prevention of mesangial proliferative glomerulonephritis.
authors: Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China.
authors: Bin
authors: B
authors: Wang
authors: Aiqing
authors: A
authors: Zhang
authors: Jun
authors: J
authors: Zheng
authors: Jing
authors: J
authors: Gong
authors: Shanwen
authors: S
authors: Li
authors: Zhifeng
authors: Z
authors: Zeng
authors: Weihua
authors: W
authors: Gan
mesh_terms: D000818:Animals; D001483:Base Sequence; D000077214:Becaplermin; D015153:Blotting, Western; D002018:Bufanolides / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D017931:DNA Primers; D005434:Flow Cytometry; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D008419:Materia Medica; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002018:Bufanolides; D017931:DNA Primers; D008419:Materia Medica; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D018844:Cyclin-Dependent Kinases; C022777:bufalin