title: Adiponectin inhibits PDGF-induced mesangial cell proliferation: regulation of mammalian target of rapamycin-mediated survival pathway by adenosine 5-monophosphate-activated protein kinase.
abstract: An aberrant proliferation of mesangial cells (MCs) is one of the more important features of diabetic nephropathy (DN). Adiponectin, an adipocyte-derived hormone, has been associated with type 2 diabetes, a known cause of DN. Recent studies have suggested that adiponectin has a protective effect on the kidney. To elucidate the potential protective mechanism of adiponectin on kidney, we investigated the effects of adiponectin on platelet-derived growth factor (PDGF)-induced cell proliferation and intracellular signaling pathways in cultured Human MCs (HMCs). PDGF-induced HMC proliferation was significantly inhibited by the co-treatment of adiponectin. Adiponectin alone had no effect on HMC proliferation. The mammalian target of rapamycin (mTOR) and 40 S ribosomal S6 kinase 1 (S6K1) were activated by PDGF stimulation in HMCs. PDGF-induced mTOR and S6K1 phosphorylations were significantly attenuated by the co-treatment of adiponectin in HMC. Adiponectin alone had no effects on PDGF-receptor autophosphorylation by PDGF. We also confirmed that the inhibitory effect of adiponectin on PDGF-induced HMC proliferation was significantly suppressed by compound C, an adenosine 5'-monophosphate-activated protein kinase (AMPK) inhibitor. From these findings, it is implied that adiponectin could attenuate renal dysfunction associated with MC disorders through AMPK-mTOR signal pathway.
authors: Department of Endocrinology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors: Y-X
authors: YX
authors: Su
authors: H-C
authors: HC
authors: Deng
authors: M-X
authors: MX
authors: Zhang
authors: J
authors: J
authors: Long
authors: Z-G
authors: ZG
authors: Peng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000494:pharmacology*; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D050527:Mesangial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D052242:Adiponectin; D020574:Proto-Oncogene Proteins c-sis; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D055372:AMP-Activated Protein Kinases