OXIDATIVE STRESS-INDUCIBLE PROTEIN-TYROSINE-PHOSPHATASE IN GLOMERULONEPHRITIS

Previously we found that rat mesangial cells express 3CH134/CL100 prot ein-tyrosine phosphatase (PTPase) in response to reactive oxygen inter mediates (ROIs), and we now extend these studies to glomerulonephritis (GN), where ROI have been demonstrated to play a role. The rat homolo gue of 3CH134/CL100 was cloned from a rat macrophage cDNA library. The rat 3CH134/CL100 mRNA was strongly induced in the lung, liver, and he art the first day after birth, suggesting that hyperoxic adaption migh t be involved in the induction of the PTPase mRNA. In anti-glomerular basement membrane (GEM) antibody (Ab) GN in rats, the 3CH134/CL100 PTP ase mRNA was expressed in glomeruli as early as 30 minutes after anti- GEM Ab injection. The 3CH134/CL100 mRNA expression was modulated by th e ROI scavenger dimethylthiourea (DMTU), indicating that its induction was ROI related. In contrast to the glomerular lesion, PTPase mRNA ex pression was not induced in experimental tubulointerstitial nephritis. In situ hybridization suggested that mesangial and some infiltrating cells were the major glomerular cell sources of the PTPase mRNA. These results indicate that rat CCH134/CL100 PTPase is actively induced in glomeruli as part of an acute immune injury at least in part related t o oxidative stress. PTPase induction in GN and potentially other forms of inflammation may play an important regulatory role in protein kina se signaling pathways.