Resveratrol alleviates sepsis-induced acute kidney injury by deactivating the lncRNA MALAT1/MiR-205 axis

Biao Wang; Yijun Wang; Ke Xu; Zhenhua Zeng; Ziqiang Xu; Dongyou Yue; Tao Li; Jihui Luo; Junhong Liu; Jiemin Yuan

doi:10.5114/ceji.2021.109195

Resveratrol alleviates sepsis-induced acute kidney injury by deactivating the lncRNA MALAT1/MiR-205 axis

Cent Eur J Immunol. 2021;46(3):295-304. doi: 10.5114/ceji.2021.109195. Epub 2021 Oct 19.

Authors

Biao Wang¹, Yijun Wang², Ke Xu², Zhenhua Zeng³, Ziqiang Xu², Dongyou Yue², Tao Li², Jihui Luo², Junhong Liu², Jiemin Yuan²

Affiliations

¹ The Second Hospital, University of South China, China.
² Chenzhou No. 1 People's Hospital, China.
³ Nanfang Hospital, Southern Medical University, China.

Abstract

Introduction: Resveratrol plays a protective role against sepsis development, and the long noncoding RNA (lncRNA) MALAT1 is an inflammation-relevant biomarker. This investigation attempted to reveal whether resveratrol attenuated inflammation of sepsis-induced acute kidney injury (AKI) by regulating MALAT1.

Material and methods: In total 120 rats were divided into a control group (n = 20), a Sham group (n = 20), a sepsis group (n = 40) and a resveratrol group (n = 40), and serum levels of inflammatory cytokines and AKI biomarkers were determined. An equal number of rats under identical treatments were, additionally, tracked for their survival, and the serum level of lncRNA MALAT1 was measured by RT-PCR. Moreover, septic cell models were constructed by treating HK-2 cells with lipopolysaccharide (LPS), and tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 levels released by the cells were determined with ELISA.

Results: Resveratrol treatment significantly brought down serum levels of inflammatory cytokines (i.e. TNF-α, IL-1β and IL-6), kidney function indicators (i.e. Scr, blood urea nitrogen [BUN] and Scys C), AKI biomarkers (i.e. NGAL and KIM-1) and MALAT1 in cecal ligation and puncture (CLP)-induced septic model rats (all p < 0.05), and the life span of septic rats was elongated by resveratrol treatment (p < 0.05). Viability and cytokine release of LPS-treated HK2 cells were rescued by resveratrol (p < 0.05), which was accompanied by a marked fall of MALAT1 expression (p < 0.05). In addition, si-MALAT1 diminished viability and suppressed cytokine release of HK2 cells, while pcDNA3.1-MALAT1 hindered the impact of resveratrol on the inflammatory response of HK2 cells (p < 0.05). Ultimately, miR-205, a protective molecule in sepsis-relevant AKI, was down-regulated by resveratrol and si-MALAT1 (p < 0.05).

Conclusions: Resveratrol relieved sepsis-induced AKI by restraining the lncRNA MALAT1/miR-205 axis.

Keywords: acute kidney injury; cell viability; inflammation; lncRNA MALAT1; miRNA-205; resveratrol; sepsis.