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Apoptosis and cell proliferation in proximal tubular cells exposed to apoptotic bodies. Novel pathophysiological implications in cisplatin-induced renal injury.
- Source :
-
Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2019 Sep 01; Vol. 1865 (9), pp. 2504-2515. Date of Electronic Publication: 2019 Jun 11. - Publication Year :
- 2019
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Abstract
- 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 (COX-2)/intracellular prostaglandin E <subscript>2</subscript> (iPGE <subscript>2</subscript> )/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 iPGE <subscript>2</subscript> in ABs-recipient HK-2 cells. Inhibition of the COX-2/iPGE <subscript>2</subscript> /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/iPGE <subscript>2</subscript> /EP receptor pathway. These results suggest that ABs, through iPGE <subscript>2</subscript> -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 iPGE <subscript>2</subscript> also mediates both cisplatin-induced HK-2 cell apoptosis, intervention in the COX-2/iPGE <subscript>2</subscript> /EP receptor pathway might provide us with new therapeutic avenues in patients with cisplatin-induced acute kidney injury.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Acute Kidney Injury metabolism
Acute Kidney Injury pathology
Cell Line
Cell Survival drug effects
Cyclooxygenase 2 chemistry
Cyclooxygenase 2 metabolism
Cyclooxygenase 2 Inhibitors pharmacology
Dinoprostone metabolism
Epithelial Cells cytology
Epithelial Cells metabolism
Humans
Kidney Tubules, Proximal cytology
Receptors, Prostaglandin E antagonists & inhibitors
Receptors, Prostaglandin E metabolism
Signal Transduction drug effects
Up-Regulation drug effects
Antineoplastic Agents toxicity
Apoptosis drug effects
Cell Proliferation drug effects
Cisplatin toxicity
Extracellular Vesicles metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-260X
- Volume :
- 1865
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. Molecular basis of disease
- Publication Type :
- Academic Journal
- Accession number :
- 31195118
- Full Text :
- https://doi.org/10.1016/j.bbadis.2019.06.008