<p>Silencing of KCNQ1OT1 Decreases Oxidative Stress and Pyroptosis of Renal Tubular Epithelial Cells</p>

Abstract

Background: Long noncoding RNAs (lncRNAs) can regulate the progression of DN. This research aimed to study the effect of lncRNA KCNQ1OT1 on the oxidative stress and pyroptosis of the renal tubular epithelial cells induced by high glucose (HG). Methods: RT-qPCR analysis detected the KCNQ1OT1 expression in serum with DN and HGinduced HK-2 cells, detect the expression of NLRP3, cleaved-caspase1, P-caspase1, IL-1β, p-IL-1β and GSDMD-N in HG-induced HK-2 cells, and confirm the transfection effects. The expression of NLRP3, cleaved-caspase1, P-caspase1, IL-1β, p-IL-1β and GSDMD-N in HGinduced HK-2 cells was also analyzed by Western blot analysis. ELISA assay detected the levels of TNF-α, IL-6 and MCP-1. The levels of ROS, MDA and SOD were determined by respective ELISA kits and ROS was also detected by the ROS assay kit (containing DCFH-DA). Results: We found that KCNQ1OT1 was increased in the plasma of patients with DN and HG-induced HK-2 cells and KCNQ1OT1 interference could decrease the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells. In addition, KCNQ1OT1 directly targets miR-506-3p. MiR-506-3p was downregulated in the plasma of patients with DN and HG-induced HK-2 cells and KCNQ1OT1 interference promoted the expression of miR-506-3p. MiR-506-3p overexpression suppressed the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells. Conclusion: This study demonstrated that downregulation of KCNQ1OT1 inhibited the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells by up-regulating the expression of miR-506-3p, which provide new insights into the treatment of DN.

Andrade-Oliveira Salvianolic Acid B Modulates Caspase-1–Mediated Pyroptosis in Renal Ischemia-Reperfusion Injury via Nrf2 Pathway

“…With the development of AKI, a large amount of ROS are produced, which leads to the activation of The NLR family pyrin domain-containing 3 (NLRP3) inflammasome and the cleavage of caspase-1, thereby promoting the maturation of inflammatory cytokines and promoting the release of interleukin (IL)-1β and IL-18 ( Kim et al, 2019 ; Zahid et al, 2019 ). The activation of cl-caspase-1 will induce caspase-1–mediated pyroptosis and aggravate renal injury ( Wang et al, 2020 ; Zhu et al, 2020 ). Nuclear factor erythroid-2 related factor 2 (Nrf2), which is a well-known transcription factor with an important role in cytoprotection, is activated under stress conditions when excessive ROS are detected ( Ungvari et al, 2019 ; Tsushima et al, 2020 ).…”

Identification of MicroRNA-92a-3p as an Essential Regulator of Tubular Epithelial Cell Pyroptosis by Targeting Nrf1 via HO-1

“…Research suggests that miRNAs are key regulators and potential biomarkers or therapeutic targets of renal IRI. These studies have also shown that miRNAs are crucial in renal IRI by regulating TEC pyroptosis ( Wu et al, 2016 ; Song et al, 2019 ; Zhu et al, 2020 ). Thus, exploring the potential mechanism of miRNAs in renal IRI can be effective in preventing AKI and its transformation into CKD and ESRD.…”

New Insights into the Mechanisms of Pyroptosis and Implications for Diabetic Kidney Disease

“…In the pyroptosis pathway, GSDMD is cleaved by inflammatory caspases at an aspartate site within the linking loop, thereby generating the self-inhibited group GSDMD-C-terminal (GSDMD-CT) and the active group GSDMD-N-terminal (GSDMD-NT) [ 32 , 33 ]. Inhibitory binding between GSDMD-NT and GSDMD-CT leads to the inactivity of GSDMD.…”

“…However, the concrete effect of GSDMD-NT on cell pore formation in tubular cells has yet to be tested. It is worthy to mention that GSDMD is critical for the secretion of mature IL-1β and IL-18 to extracellular environment, independent of NLRP3 inflammasome and caspase-1 [ 33 ], which indicates that it might be insufficient to simply inhibit NLRP3 inflammasome or caspase-1 in pyroptosis pathway. Actually, the molecular mechanisms of GSDMD in pyroptosis have been relatively clear, but novel discoveries of the correlation between pyroptosis and DKD may inspire us to explore more about GSDMD’s effects in kidneys.…”