title: Betulinic acid inhibits cell proliferation and fibronectin accumulation in rat glomerular mesangial cells cultured under high glucose condition.
abstract: Glomerular mesangial cells (MCs) proliferation and extracellular matrix (ECM) accumulation have been recognized as major pathogenic events in the progression of diabetic nephropathy. Betulinic acid (BA), (3β-hydroxy-lup-20(29)-en-28-oic acid), is a naturally occurring pentacyclic lupane group triterpenoid, and it has been shown to possess glucose-lowering property. However, the role of BA on MC proliferation and ECM accumulation in diabetic condition remains unclear. So, in the present study, we investigated the role of BA on cell proliferation and ECM accumulation in rat glomerular MCs cultured under high glucose (HG) condition. In the current study, we demonstrated that BA suppressed HG-induced MC proliferation, arrested HG-induced cell-cycle progression, reversed HG-inhibited expression of p21(Waf1/Cip1) and p27(Kip1). It also suppressed HG-induced fibronectin (FN) expression in MCs. Furthermore, BA inhibited HG-induced phosphorylation of ERK1/2 and p38MAPK in MCs. In conclusion, our present study demonstrated that BA inhibited HG-induced cell proliferation and FN expression in MCs via inhibiting ERK1/2 and p38MAPK pathways. Thus, BA may serve as a potential drug for the treatment of diabetic nephropathy.
authors.affiliation: Department of Endocrinology, Xianyang Central Hospital, Xianyang 712000, China. Electronic address: liu_chunmeidc@sina.com.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Xianyang Central Hospital, Xianyang 712000, China.
authors.forename: Xue-Lin
authors.initials: XL
authors.lastname: Qi
authors.affiliation: Department of Endocrinology, Xianyang Central Hospital, Xianyang 712000, China.
authors.forename: Ya-Feng
authors.initials: YF
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Xianyang Central Hospital, Xianyang 712000, China.
authors.forename: Xiu-de
authors.initials: XD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D050527:Mesangial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D053978:Pentacyclic Triterpenes; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D014315:Triterpenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000094062:Betulinic Acid
chemical_list: D018797:Cell Cycle Proteins; D005353:Fibronectins; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D000094062:Betulinic Acid
keywords: Betulinic acid; Diabetic nephropathy; Fibronectin; Mesangial cells (MCs)