Modelling the effects of vascular stress in mesangial cells

It has recently been shown that mesangial cells are subjected to multiple f orms of mechanical strain (fluid shear, hydrostatic pressure, and triaxial stretch) as a result of forces exerted by the vasculature. Nevertheless, th e exact nature and the relative response to these stimuli have not been cla rified. Although it is now well established that cyclic stretching of mesan gial cells in culture results in the overproduction of extracellular matrix , indicating how intraglomerular hypertension may lead to glomerular scar f ormation, 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, transformi ng 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 f or protein kinase C, recent studies also implicate the mitogen-activated pr otein kinases along with enhanced DNA-binding activity of AP-1 as part of t he signalling cascade altering matrix synthesis and cell proliferation in r esponse to stretch, Finally, recent studies examining the effects of oscill ating hyperbaric pressure demonstrate similarities, as well as differences, in comparison to those of cyclic stretch, Cun Opin Nephrol Hypertens 9:43- 47, (C) 2000 Lippincott Williams & Wilkins.