PROTEASE NEXIN-1 IN THE MURINE KIDNEY - GLOMERULAR LOCALIZATION AND UP-REGULATION IN GLOMERULOPATHIES

Protease nexin 1 (PN-1). a potent serpin-class antiprotease, is though t to be synthesized in the murine kidney. However, neither the cellula r localization of PN-1 synthesis nor its role has as vet been defined. To address these questions, we determined by ill situ hybridizations RNase protection assay and immunoblotting, the sites of PN-1 mRNA accu mulation in normal mouse kidneys and the modulation of PN-1 expression in several pathological conditions. In normal kidneys. PN-1 mRNA was detected primarily in glomeruli, most likely in mesangial cells. The g lomerular expression of PN-1 was substantially enhanced not only in lu pus-like glomerulonephritis (induced by IgG3 monoclonal rheumatoid fac tors or occurring spontaneously in lupus-prone mice), but also in mild glomerular lesions associated with intracapillary thrombi induced by IgG3 anti-trinitrophenyl monoclonal antibodies. In contrast, no modula tion of PN-1 mRNA levels was observed during the course of lipopolysac charide-induced acute tubular necrosis. A constitutive PN-1 gene expre ssion and its up-regulation during glomerular injury suggest a possibl e role for PN-1 in glomerular biology. In view of its high inhibitory activity towards thrombin, mesangial PN-1 may be involved in the contr ol of glomerular coagulation following initial glomerular injuries.