Modelling the effects of vascular stress in mesangial cells : Current Opinion in Nephrology and Hypertension (original) (raw)

Review Article

Department of Internal Medicine, Division of Nephrology, Henry Ford Hospital, Detroit, MI, USA

Correspondence to Bruce L. Riser, AB, MS, PhD, Henry Ford Hospital, Division of Nephrology and Hypertension, CPF-509, 2799 West Grand Boulevard, Detroit, MI 48202, USA. Tel: +1 313 876 2145; fax: +1 313 876 2554; e-mail: [email protected]

Abbreviations

CTGF: connective tissue growth factor

ECM: extracellular matrix

ERK: extracellular signal-regulated kinase

JNK: c-Jun NH2-terminal kinase

MAPK: mitogen-activated protein kinase

MEK: mitogen-activated protein kinase or extracellular signal-regulated : kinase

MC: mesangial cells

PTK: protein tyrosine kinase

PKC: protein kinase C

TGF-β: transforming growth factor beta

VEGF: vascular endothelial growth factor

Abstract

It has recently been shown that mesangial cells are subjected to multiple forms of mechanical strain (fluid shear, hydrostatic pressure, and triaxial stretch) as a result of forces exerted by the vasculature. Nevertheless, the exact nature and the relative response to these stimuli have not been clarified. Although it is now well established that cyclic stretching of mesangial cells in culture results in the overproduction of extracellular matrix, indicating how intraglomerular hypertension may lead to glomerular scar formation, the contribution of different intracellular signalling mechanisms and extracellular mediators of the response are only now being identified. Recent studies point to a role for high glucose concentrations, transforming growth factor beta and its receptors, vascular endothelial growth factor, and connective tissue growth factor as important mediators, or modifiers of the response to mechanical strain. Although evidence exists for a role for protein kinase C, recent studies also implicate the mitogen-activated protein kinases along with enhanced DNA-binding activity of AP-1 as part of the signalling cascade altering matrix synthesis and cell proliferation in response to stretch. Finally, recent studies examining the effects of oscillating hyperbaric pressure demonstrate similarities, as well as differences, in comparison to those of cyclic stretch.