Inhibitory effects of adiponectin on platelet-derived growth factor-induced mesangial cell migration

J Endocrinol. 2009 Aug;202(2):309-16. doi: 10.1677/JOE-08-0469. Epub 2009 May 21.

Abstract

Adiponectin, an adipocyte-derived hormone, has been involved in metabolic syndrome, a known risk factor for the development of chronic kidney disease (CKD). Recent studies have demonstrated that plasma adiponectin levels are elevated when kidney function declines in patients with CKD. Excessive mesangial cell (MC) turnover is one of the important features of CKD. The aim of the present study is to elucidate the effects of adiponectin on platelet-derived growth factor (PDGF)-induced cell migration and intracellular signaling pathways, in cultured rat MCs (RMCs). PDGF-induced RMC migration was significantly inhibited by the pretreatment of adiponectin. Adiponectin alone had no effect on RMC migration. Big mitogen-activated protein (MAP) kinase 1 (BMK1), p38 MAP kinase, and Akt were activated by PDGF stimulation in a time- and concentration-dependent manner in RMC. Adiponectin alone did not affect BMK1, p38 MAP kinase, and Akt phosphorylations in RMC. PDGF-induced BMK1 and p38 MAP kinase phosphorylations were significantly attenuated by the pretreatment of adiponectin in RMCs. On the other hand, the phosphorylation of Akt by PDGF was not diminished by the pretreatment of adiponectin. Adiponectin had no effects on PDGF-receptor autophosphorylation by PDGF. We also confirmed that PDGF-induced RMC migration was significantly suppressed by siBMK1 transfection or SB203580, a p38 MAP kinase inhibitor. From these findings, it is implied that the elevated plasma adiponectin levels in patients with CKD might play a compensatory role aimed at counteracting renal dysfunction related to MC disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / administration & dosage
  • Adiponectin / pharmacology*
  • Animals
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Glomerular Mesangium / cytology*
  • Glomerular Mesangium / physiology*
  • Imidazoles / pharmacology
  • Male
  • Mitogen-Activated Protein Kinase 7 / genetics
  • Mitogen-Activated Protein Kinase 7 / metabolism
  • Phosphorylation / drug effects
  • Platelet-Derived Growth Factor / administration & dosage
  • Platelet-Derived Growth Factor / pharmacology*
  • Pyridines / pharmacology
  • RNA, Small Interfering / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Adiponectin
  • Enzyme Inhibitors
  • Imidazoles
  • Platelet-Derived Growth Factor
  • Pyridines
  • RNA, Small Interfering
  • Recombinant Proteins
  • Mitogen-Activated Protein Kinase 7
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580