PROLIFERATING AND MIGRATING MESANGIAL CELLS RESPONDING TO INJURY EXPRESS A NOVEL RECEPTOR PROTEIN-TYROSINE-PHOSPHATASE IN EXPERIMENTAL MESANGIAL PROLIFERATIVE GLOMERULONEPHRITIS

The mesangial cell provides structural support to the kidney glomerulu s, A polymerase chain reaction-based cDNA display approach identified a novel protein-tyrosine phosphatase, rPTP-GMC1, whose transcript expr ession is transiently and dramatically up-regulated during the period of mesangial cell migration and proliferation that follows mesangial c ell injury in the anti-Thy 1 model of mesangial proliferative glomerul onephritis in the rat. In situ hybridization analysis confirmed that r PTP-GMC1 mRNA is up-regulated specifically by mesangial cells respondi ng to the injury and is not detectable in other cells in the kidney or in many normal tissues. In cell culture, rPTP-GMC1 is expressed by me sangial cells but not by glomerular endothelial or epithelial cells (p odocytes), The longest transcript (7.5 kilobases) encodes a receptor-l ike protein-tyrosine phosphatase consisting of a single catalytic doma in, a transmembrane segment, and 18 fibronectin type like repeats in t he extracellular segment. A splice variant predicts a truncated molecu le missing the catalytic domain. rPTP-GMC1 maps to human chromosome 12 q15 and to the distal end of mouse chromosome 10, The predicted struct ure of rPTP-GMC1 and its pattern of expression in vivo and in culture suggest that it prays a role in regulating the adhesion and migration of mesangial cells in response to injury.