HucMSC exosomes-delivered 14-3-3ζ enhanced autophagy via modulation of ATG16L in preventing cisplatin-induced acute kidney injury.

Abstract

The clinical application of cisplatin is restricted by its side effects of nephrotoxicity. Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-ex) have an important effect in tissue injury repair. Our previous work discovered that pretreatment with human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-ex) alleviated cisplatin-induced acute kidney injury (AKI) by activating autophagy both in vitro and in vivo. In this study, we further explored the mechanisms of hucMSC-ex in autophagy for preventing cisplatin-induced nephrotoxicity. We discovered that 14-3-3ζ was contained in hucMSC-ex, and knockdown and overexpression 14-3-3ζ reduced and enhanced the autophagic activity respectively. Furthermore, Knockdown of 14-3-3ζ alleviated the preventive effect of hucMSC-ex. In contrast, overexpression of 14-3-3ζ enhanced the effect. Further results confirmed that hucMSC-ex increased ATG16L expression and that 14-3-3ζ interacted with ATG16L, promoting the localization of ATG16L at autophagosome precursors. In this study, we revealed that hucMSC-ex-delivered 14-3-3ζ interacted with ATG16L to activate autophagy. Our findings suggest that 14-3-3ζ is a novel mechanism for MSC-exosomes-activated autophagy and provides a new strategy for the prevention of cisplatin-induced nephrotoxicity.

• Authors: Haoyuan Jia, Wanzhu Liu, Bin Zhang, Juanjuan Wang, Peipei Wu, Nitin Tandra, Zhaofeng Liang, Cheng Ji, Lei Yin, Xinyuan Hu, Yongmin Yan, Fei Mao, Xu Zhang, Jing Yu, Wenrong Xu, Hui Qian
• Journal: American journal of translational research (Am J Transl Res) Vol. 10 Issue 1 Pg. 101-113 ( 2018) ISSN: 1943-8141 [Print] United States
• PMID: 29422997 (Publication Type: Journal Article)