Loss of Rictor in tubular cells exaggerates lipopolysaccharide induced renal inflammation and acute kidney injury via Yap/Taz-NF-κB axis

Yuan Gui; Qing Hou; Qingmiao Lu; Chunsun Dai; Jianzhong Li

doi:10.1038/s41420-020-0274-3

Loss of Rictor in tubular cells exaggerates lipopolysaccharide induced renal inflammation and acute kidney injury via Yap/Taz-NF-κB axis

Cell Death Discov. 2020 May 29:6:40. doi: 10.1038/s41420-020-0274-3. eCollection 2020.

Authors

Yuan Gui^{1

2}, Qing Hou¹, Qingmiao Lu¹, Chunsun Dai¹, Jianzhong Li³

Affiliations

¹ Center for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu 210003 China.
² Division of Nephrology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242 USA.
³ Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006 China.

Abstract

Our previous study demonstrated that the mammalian target of rapamycin complex 2 (mTORC2) signaling alleviates renal inflammation and protects against cisplatin-induced AKI. However, the underlying mechanisms for mTORC2 in regulating renal inflammation in AKI remain to be determined. In this study, we found that lipopolysaccharide (LPS) could activate mTORC2 signaling in NRK-52E cells, and blockage of mTORC2 signaling led to Yap/Taz degradation, which in turn activated NF-κB signaling and induced inflammatory cytokines secretion. Overexpression of constitutively active Taz (Taz-S89A) could attenuate the inflammation-amplified role of mTORC2 blockage. In mouse models, tubule-specific deletion of Rictor had higher blood urea nitrogen level, severe morphological injury as well as more inflammatory cells accumulation compared with those in their littermate controls. Overall, these results demonstrate that mTORC2 signaling protects against renal inflammation and dictates the outcome of AKI by modulating Yap/Taz degradation.

Keywords: Acute kidney injury; Mechanisms of disease.