Mesangial proliferative glomerulonephritis (MPGN) is characterized by mesangial cells (MC) inflammation, proliferation and apoptosis. The parathyroid hormone-related protein (PTHrP) is known to influence these processes in many cell types. In this work we analyzed the effects of PTHrP on MC proliferation, apoptosis and inflammation. Our results show that PTHrP induced MC proliferation through the intracrine pathway while it promoted their survival through the paracrine one. PTHrP activating its receptor PTH1R, led to the activation of cAMP/PKA and PI3-K/Akt pathways, which induced NF-kappaB, and upregulated the cyclooxygenase-2 (Cox-2). We have shown that the Cox-2 was responsible of the anti-apoptotic effect of PTHrP on MC. Otherwise, IL-1beta and TNF-alpha importantly upregulated the PTHrP in MC and PTHrP itself led to an overexpression of many cytokines and chemokines. The overexpression of cytokines (IL-17 and IL-16) was brief (2h) while that of chemokines was extended (4h). In a mouse model of MPGN, PTHrP was upregulated in the injured glomeruli at day 1. PTHrP may then contribute to the inflammation, the proliferation and the survival of MC.
