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

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.

Disease-Associated Regulation of Non-Coding RNAs by Resveratrol: Molecular Insights and Therapeutic Applications

“…Resveratrol seems to modulate several miRNAs involved in inflammatory pathways, such as the proinflammatory miR-155, the anti-inflammatory miR-663, and the oncogenic miR-21 21 ( Latruffe et al, 2015 ). A recent study has also reported the potential involvement of the lncRNA MALAT-1, a biomarker of inflammation ( Wang et al, 2021 ). Treatment with resveratrol in rats with sepsis-induced kidney damage was associated with lower circulating concentrations of this lncRNA compared to untreated animals ( Wang et al, 2021 ).…”

“…A recent study has also reported the potential involvement of the lncRNA MALAT-1, a biomarker of inflammation ( Wang et al, 2021 ). Treatment with resveratrol in rats with sepsis-induced kidney damage was associated with lower circulating concentrations of this lncRNA compared to untreated animals ( Wang et al, 2021 ). Moreover, resveratrol reduced the intracellular concentrations of key pro-inflammatory cytokines, i.e., TNF-α, IL-1β and IL-6 ( Wang et al, 2021 ).…”

“…Treatment with resveratrol in rats with sepsis-induced kidney damage was associated with lower circulating concentrations of this lncRNA compared to untreated animals ( Wang et al, 2021 ). Moreover, resveratrol reduced the intracellular concentrations of key pro-inflammatory cytokines, i.e., TNF-α, IL-1β and IL-6 ( Wang et al, 2021 ). Based on previous studies reporting the participation of several MALAT1-sponged miRNAs, including miR-205 and miR204, in the pathogenesis of acute kidney injury (AKI) ( Li et al, 2016 ; Chen et al, 2018 ), Wang et al investigated the potential involvement of these miRNAs in their model of sepsis-induced AKI and the effects of resveratrol ( Wang et al, 2021 ).…”

“…Moreover, resveratrol reduced the intracellular concentrations of key pro-inflammatory cytokines, i.e., TNF-α, IL-1β and IL-6 ( Wang et al, 2021 ). Based on previous studies reporting the participation of several MALAT1-sponged miRNAs, including miR-205 and miR204, in the pathogenesis of acute kidney injury (AKI) ( Li et al, 2016 ; Chen et al, 2018 ), Wang et al investigated the potential involvement of these miRNAs in their model of sepsis-induced AKI and the effects of resveratrol ( Wang et al, 2021 ). Resveratrol downregulated miR-205 expression, suggesting that the inhibition of the lncRNA MALAT1/miR-205 axis by this flavonoid protects against sepsis-induced AKI ( Wang et al, 2021 ).…”

“…Based on previous studies reporting the participation of several MALAT1-sponged miRNAs, including miR-205 and miR204, in the pathogenesis of acute kidney injury (AKI) ( Li et al, 2016 ; Chen et al, 2018 ), Wang et al investigated the potential involvement of these miRNAs in their model of sepsis-induced AKI and the effects of resveratrol ( Wang et al, 2021 ). Resveratrol downregulated miR-205 expression, suggesting that the inhibition of the lncRNA MALAT1/miR-205 axis by this flavonoid protects against sepsis-induced AKI ( Wang et al, 2021 ). High-throughput RNA sequencing of chondrocytes treated with the pro-inflammatory factor IL-1beta, in presence or absence of resveratrol, revealed several differentially expressed lncRNAs, miRNAs, and mRNAs.…”