P2 receptor antagonist PPADS inhibits mesangial cell proliferation in experimental mesangial proliferative XXXX .

@entity644 @entity8 @entity1133 @entity1423 @entity2036 @entity38557 @entity12702 @entity377 @entity12700 @entity665 @entity7622 @entity1011 @entity35 @entity631 @entity18715
BACKGROUND: Although extracellular @entity2036 have been shown to confer mitogenic effects in cultured @entity35 mesangial cells through activation of purinergic P2 receptors (P2Y receptors), thus far the in vivo relevance of these findings is unclear. Virtually all cells and in particular the dense granules of platelets contain high levels of @entity2036 that are released upon cell injury or @entity1423 . In experimental mesangial proliferative @entity631 in the rat (anti- @entity18715 model), mesangiolysis and glomerular @entity1423 are followed by a pronounced mesangial cell (MC) proliferative response leading to @entity8 . Therefore, we examined the role of extracellular @entity2036 and their corresponding receptors in @entity377 -stimulated cultured mesangial cells and in @entity8 using the P2 receptor antagonist PPADS. METHODS: The effects of @entity38557 on @entity377 - or fetal calf serum (FCS)-stimulated proliferation of cultured MC were measured by cell counting and @entity665 incorporation assay. After induction of the anti- @entity18715 model, @entity35 received injections of the P2-receptor antagonist PPADS at different doses (15, 30, 60 mg/kg BW). Proliferating mesangial and non-mesangial cells, mesangial cell activation, matrix accumulation, influx of inflammatory cells, mesangiolysis, microaneurysm formation, and renal functional parameters were assessed during anti- @entity18715 disease. P2Y-mRNA and protein expression was assessed using RT-PCR and real time PCR, Northern blot analysis, in situ hybridization, and immunohistochemistry. RESULTS: In cultured mesangial cells, PPADS inhibited @entity377 , but not FCS-stimulated proliferation in a dose-dependent manner. In the anti- @entity18715 model, PPADS specifically and dose-dependently reduced early (day 3), but not late (day 8), glomerular mesangial cell proliferation as well as phenotypic activation of the mesangium and slightly matrix expansion. While no consistent effect was obtained in regard to the degree of mesangiolysis, influx of inflammatory cells, @entity644 or blood pressure, PPADS treatment increased serum @entity1011 and @entity1133 in anti- @entity18715 @entity35 . P2Y receptor expression ( @entity12700 and @entity12702 ) was detected in cultured MC and isolated glomeruli, and demonstrated a transient marked increase during anti- @entity18715 disease. CONCLUSION: These data strongly suggest an in vivo role for extracellular @entity2036 in mediating early MC proliferation after @entity7622 .
