Nephrotoxicity is a major adverse effect of cisplatin-mediated chemotherapy in cancer patients. The pathogenesis of cisplatin-induced nephrotoxicity remains largely unclear, making it difficult to design effective renoprotective approaches. Here, we have examined the role of microRNAs (miRNAs) in cisplatin-induced nephrotoxicity. We show that cisplatin nephrotoxicity was not affected by overall depletion of both beneficial and detrimental miRNAs from kidney proximal tubular cells in mice in which the miRNA-generating enzyme Dicer had been conditionally knocked out. To identify miRNAs involved in cisplatin nephrotoxicity, we used microarray analysis to profile miRNA expression and identified 47 up- regulated microRNAs and 20 down-regulated microRNAs in kidney cortical tissues. One up-regulated miRNA was miR-375, whose expression was also induced in cisplatin-treated renal tubular cells. Interestingly, inhibition of miR-375 decreased cisplatin-induced apoptosis, suggesting that miR-375 is a cell-damaging or pro-apoptotic agent. Blockade of p53 or NF-κB attenuated cisplatin-induced miR-375 expression, supporting a role of p53 and NF-κB in miR-375 induction. We also identified hepatocyte nuclear factor 1 homeobox B (Hnf-1β) as a key downstream target of miR-375. Of note, we further demonstrated that Hnf-1β protected renal cells against cisplatin-induced apoptosis. Together, these results suggest that upon cisplatin exposure, p53 and NF-κB collaboratively induce miR-375 expression, which, in turn, represses Hnf-1β activity, resulting in renal tubular cell apoptosis and nephrotoxicity.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2jXAa1j
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
Publication date: March 2017 Source: Free Radical Biology and Medicine, Volume 104 from #AlexandrosSfakianakis via Alexandros G.Sfak...
-
Dtsch med Wochenschr DOI: 10.1055/s-0043-100054 Hintergrund und Fragestellung Ein etablierter Weg, die optimale Behandlung von Tumorpatien...
-
Background Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extrac...
-
Deepak Thapa, Vanita Ahuja, Deepanshu Dhiman Indian Journal of Anaesthesia 2017 61(12):1012-1014 from #AlexandrosSfakianakis via Alexa...
-
Abstract Limited memory size is considered as a major bottleneck in data centers for intelligent urban computing. It is shown that there e...
-
ecancer is supporting #BowelCancerAwarenessMonth https://t.co/opXxCAAxzE from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inore...
-
Linked Article: Maintz et al. Br J Dermatol 2017; 176:481–487 . from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader h...
-
Angelina Jolie’s openness about her diagnosis has undoubtedly raised public awareness of the importance of inherited cancers. Although Desai...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου