Cytosolic and nuclear signaling by endothelin peptides: Mesangial response to glomerular injury

Cell signaling plays an important role in directing the phenotypic changes that mesangial cells undergo in glomerular disease. These changes include increased synthesis and reorganization of extracellular matrix, protease secretion, processing of extracellular macromolecules such as immune complexes, and cell growth in the form of hypertrophy and hyperplasia [1]. Although rearrangements or mutations in the mesangial genome might account for some of these phenotypic alterations, it is now clear that many of these changes result from regulation of gene expression by extracellular ligands. Proinflammatory ligands, such as growth factors, cytokines, and peptides, evoke a network of short-term signals that are extended to long-term events involving differential regulation of gene expression. But despite recent advances, the pathways of signaling by which these ligands regulate the genetic program of mesangial cells remain unclear