Mechanical stretch-induced signal transduction in cultured mesangial cells.

The investigation of the effects of mechanical stretch on mesangial cells can provide important insights into glomerular pathophysiology related to increased intraglomerular pressure (Pgc). Elevated Pgc, leading to the transmission of abnormal mechanical stress to resident renal glomerular cells, is a major pathogenic factor in progressive glomerular fibrosis and the ultimate loss of renal function. Mesangial cells, at the center of the glomerular tuft, produce extracellular matrix components when exposed to mechanical stretch, thus providing a model system simulating in vivo pathology. Stretch-induced activation of the mitogen-activated protein kinase Erk has been linked to matrix production. The integrity of the actin cytoskeleton, an important transmitter of mechanical signals, is required for activation of Erk and its upstream kinase Raf-1. The GTPase RhoA, a central regulator of the actin cytoskeleton, is also activated by stretch, and both Erk activation and subsequent matrix upregulation are dependent on its function. The investigation of signaling pathways activated by mechanical stretch and associated with abnormal matrix production or regulation will assist in the development of new therapies targeted at slowing the progression of renal disease.