Implications of miRNAs on TGF- β/TAK1/mTOR pathway in mediating the renoprotective effects of pentoxifylline against cisplatin-induced nephrotoxicity in rats.

Implications of miRNAs on TGF-β/TAK1/mTOR pathway in mediating the renoprotective effects of pentoxifylline against cisplatin-induced nephrotoxicity in rats. Toxicol Appl Pharmacol. 2020 Aug 07;:115184 Authors: El Magdoub HM, Schaalan MF, Rahmo RM, Farag DB, Khedr LH Abstract CIS-mediated nephrotoxicity is induced via transforming growth factor-beta (TGF-β) and TGF-β-activated kinase (TAK1). TGF-β and TAK1 are known to interact with microRNA-let-7b and microRNA-26b, respectively. Additionally, TGF-β1 is reported to down-regulate the autophagy marker microtubule-associated protein 1 light chain 3-II (LC3-II) through upregulation of microRNA-34a. Pentoxifylline (PTX) anti-inflammatory effects are mediated via suppressing TGF-β and regulating mammalian target of rapamycin (mTOR). The current study aimed to investigate the involvement of microRNAs let-7b, 26-b and 34a, and the modulating impact of PTX on CIS-induced nephrotoxicity. Moreover, we aimed at examining the ability of PTX to interact with TGF-β receptor-1 (TGFβR-1) and TAK1, and examine its ability to downgrade the previously reported toxicities. Hence, the expression of the aforementioned microRNAs, and protein levels of TGFβR-1, TGF-β1, TAK1, mTOR, LC3-II, and NF-κB were assessed. Molecular docking studies of PTX on TGFβR-1 and TAK1 were also executed. CIS induced TGF-β1, with down-regulation of microRNA-let-7b and -26b, and up-regulation of microRNA-34a. TGFβR-...
Source: Toxicology and Applied Pharmacology - Category: Toxicology Authors: Tags: Toxicol Appl Pharmacol Source Type: research