Angiotensin II- and glucose-stimulated extracellular matrix production: mediation by the insulin-like growth factor (IGF) axis in a murine mesangial cell line
- 8 April 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Endocrine
- Vol. 33 (1), 32-39
- https://doi.org/10.1007/s12020-008-9055-0
Abstract
In diabetic nephropathy, glomerular mesangial cells exhibit aberrant anabolic activity that includes excessive production of extracellular matrix (ECM) proteins, leading to crowding of filtration surface areas and possible renal failure. In the present study, a murine mesangial cell line (MES-13 cells) was studied to determine the roles of the renin-angiotensin system (RAS) and the insulin-like growth factor (IGF) axis in the anabolic response to elevated glucose levels. Culture of MES-13 cells in medium containing supra-physiological glucose concentrations (>5.5 mmol/l) resulted in increased production of ECM proteins including laminin, fibronectin, and heparan sulfate proteoglycan with concurrent increases in IGF-binding protein (IGFBP)-2 production. These responses were blocked by the angiotensin receptor antagonists saralasin and losartan, while exogenous angiotensin II (Ang II) treatment directly stimulated increases in ECM and IGFBP-2. In all experiments, IGFBP-2 levels were correlated with anabolic activity implicating IGFBP-2 as a possible mediator in cellular responses to high glucose and Ang II. Such mediation appears to involve IGFBP-2 modulation of IGF-I signaling, since all responses to high glucose or Ang II were blocked by immuno-neutralization of IGF-I. These data suggest alterations in the IGF axis as key mechanisms underlying nephropathic responses of mesangial cells to Ang II and high glucose.Keywords
This publication has 65 references indexed in Scilit:
- Novel roles of the IGF–IGFBP axis in etiopathophysiology of diabetic nephropathyDiabetes Research and Clinical Practice, 2007
- Renal fibrosis: New insights into the pathogenesis and therapeuticsKidney International, 2006
- Activated IGF-1R inhibits hyperglycemia-induced DNA damage and promotes DNA repair by homologous recombinationAmerican Journal of Physiology-Renal Physiology, 2005
- High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cellsAmerican Journal of Physiology-Renal Physiology, 2004
- Expression and regulation of the insulin-like growth factor axis components in rat liver myofibroblastsJournal of Cellular Physiology, 2004
- Mechanism of Increased Angiotensin II Levels in Glomerular Mesangial Cells Cultured in High GlucoseJournal of the American Society of Nephrology, 2003
- Role of angiotensin II in diabetic nephropathyKidney International, 2000
- Characterization of insulin-like growth factor binding proteins and regulation of IGFBP3 in human mesangial cellsKidney International, 1996
- Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells.JCI Insight, 1994
- Gene expression of metalloproteinase and its inhibitor in mesangial cells exposed to high glucoseBiochemical and Biophysical Research Communications, 1992