DE-NOVO CD44 EXPRESSION BY PROLIFERATING MESANGIAL CELLS IN RAT ANTI-THY-1 NEPHRITIS

CD44 is the major cell-surface receptor for hyaluronan, and cell-matri x interactions mediated by the CD44/hyaluronan receptor-ligand pair ar e involved in a variety of cellular functions, including cell migratio n, The aim of the study presented here was to examine the expression o f CD44 and hyaluronan in the mesangial proliferative response in rat a nti-Thy-1 nephritis. In normal rat kidney, CD44, is expressed by medul lary tubules, some distal tubules and thick ascending limbs of Henle d endritic-like cells around Bowman's capsule, and some interstitial cel ls, However, only occasional CD44(+) cells were found within the glome rular tuft. In experimental nephritis, there was an early glomerular i nflux of CD44(+) macrophages, which peaked on Day 4 after anti-Thy-1 a ntibody injection, A striking finding was de novo CD44 expression by m esangial cells, This CD44 expression was restricted to the transient p eriod of mesangial cell proliferation as shown by double-staining with an antibody against the proliferating cell nuclear antigen. Immunohis tochemistry staining also demonstrated hyaluronan deposition within se gmental areas of proliferating CD44(+) cells, suggesting a functional interaction between the CD44/hyaluronan receptor-ligand pair during me sangial cell proliferation. In vitro, rat mesangial cells were shown t o express mRNA and protein for the 90-kd isoform of CD44. in addition, hyaluronan-dependent aggregation of CD44(+) mesangial cells was speci fically inhibited by an anti-CD44 antibody, demonstrating a functional interaction between hyaluronan and the CD44 expressed on the surface of rat mesangial cells, In conclusion, these data suggest that cell-ma trix interactions mediated by the CD44/hyaluronan receptor-ligand pair are involved in mesangial cell proliferation in rat anti-Thy-1 nephri tis.