RT info:eu-repo/semantics/article T1 B_Apoptosis and cell proliferation in proximal tubular cells exposed to apoptotic bodies. Novel pathophysiological implications in cisplatin-induced renal injury A1 García Pastor, Coral A1 Blázquez-Serra, Rafael A1 Bosch Martínez, Ricardo José A1 Lucio Cazaña, Francisco Javier de A1 Fernández Martínez, Ana Belén K1 Apoptotic bodies K1 Cisplatin K1 Intracellular prostaglandin E2 K1 Proximal tubular cells K1 Medicina K1 Medicine AB The therapeutic efficacy of the antineoplastic drug cisplatin is limited by its nephrotoxicity, which affects particularly to proximal tubular cells (PTC). Cisplatin-induced cytotoxicity appears to be multifactorial and involves inflammation, oxidative stress as well as apoptosis. We have recently shown that the cyclo-oxygenase-2 (COX2)/intracellular prostaglandin E2 (iPGE2)/EP receptor pathway mediates the apoptotic effect of cisplatin on human proximal tubular HK-2 cells. Here, we studied the effects on HK-2 cells of apoptotic bodies (ABs) generated after treatment of HK-2 cells with cisplatin. We found that ABs inhibited cell growth, induced apoptosis and increased COX-2 expression and iPGE2 in ABs-recipient HK-2 cells. Inhibition of the COX-2/iPGE2/EP receptor pathway in these cells prevented the effects of ABs without interfering with their internalization. Interestingly, 2nd generation ABs (i.e. ABs released by cells undergoing apoptosis upon treatment with ABs) did not trigger apoptosis in naïve HK-2 cells, and stimulated cell proliferation through the COX-2/iPGE2/EP receptor pathway. These results suggest that ABs, through iPGE2-dependent mechanisms, might have a relevant role in the natural history of cisplatin-induced acute kidney failure because they contribute first to the propagation of the noxious effects of cisplatin to non-injured PTC and then to the promotion of the proliferative tubular response required for proximal tubule repair. Since iPGE2 also mediates both cisplatin-induced HK-2 cell apoptosis, intervention in the COX-2/iPGE2/EP receptor pathway might provide us with new therapeutic avenues in patients with cisplatin-induced acute kidney injury. SN 0925-4439 YR 2019 FD 2019-06-11 LK http://hdl.handle.net/10017/50417 UL http://hdl.handle.net/10017/50417 LA eng NO Ministerio de Ciencia e Innovación DS MINDS@UW RD 29-mar-2024