LncRNA KCNQ1OT1 (potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1) aggravates acute kidney injury by activating p38/NF-κB pathway via miR-212-3p/MAPK1 (mitogen-activated protein kinase 1) axis in sepsis

Abstract

Acute kidney injury (AKI), a common complication of sepsis, is characterized by a rapid loss of renal excretory function. A variety of etiologies and pathophysiological processes may contribute to AKI. Previously, mitogen-activated protein kinase 1 (MAPK1) was reported to regulate cellular processes in various sepsis-associated diseases. The current study aimed to further explore the biological function and regulatory mechanism of MAPK1 in sepsis-induced AKI. In our study, MAPK1 exhibited high expression in the serum of AKI patients. Functionally, knockdown of MAPK1 suppressed inflammatory response, cell apoptosis in response of lipopolysaccharide (LPS) induction in HK-2 cells. Moreover, MAPK1 deficiency alleviated renal inflammation, renal dysfunction, and renal injury in vivo . Mechanistically, MAPK1 could activate the downstream p38/NF-κB pathway. Moreover, long noncoding RNA potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) was identified to serve as a competing endogenous RNA for miR-212-3p to regulate MAPK1. Finally, rescue assays indicated that the inhibitory effect of KCNQ1OT1 knockdown on inflammatory response, cell apoptosis, and p38/NF-κB pathway was reversed by MAPK1 overexpression in HK-2 cells. In conclusion, KCNQ1OT1 aggravates acute kidney injury by activating p38/NF-κB pathway via miR-212-3p/MAPK1 axis in sepsis. Therefore, KCNQ1OT may serve as a potential biomarker for the prognosis and diagnosis of AKI patients.

Human bone marrow mesenchymal stem cell-derived extracellular vesicles reduce inflammation and pyroptosis in acute kidney injury via miR-223-3p/HDAC2/SNRK

“…An AKI cell model in HK-2 cells was developed with reference to the description of previous literature [ 21 ]. Briefly, the cell culture medium was supplemented with lipopolysaccharide (LPS, 1 µg/mL, Sigma-Aldrich) and then incubated with HK-2 cells for 24 h to induce inflammation before the cells were seeded onto 60 mm culture plates (1 × 10 6 cells/mL) and incubated for 16 h at 37 °C.…”

MicroRNA (miR)-590-3p alleviates high-glucose induced renal tubular epithelial cell damage by targeting C-X3-C motif chemokine ligand 1 (CX3CL1) in diabetic nephropathy

“…Subsequently, miR-590-3p mimic and mimic NC were co-transfected with recombinant plasmids into HK-2 cells. After 48 h, the luciferase activity was examined using the dual-luciferase assay system (Promega, USA) based on previous studies [ 24 ], and the ranilla luciferase was normalized.…”

MicroRNAs in septic acute kidney injury

“…NF-κB activity was shown to be inhibited in HK-2 cells transfected with miR-146b mimics through the targeting of IL-1 receptor-associated kinase (IRAK1) [ 57 ]. miR-212-3p overexpression suppressed cell apoptosis by reducing the levels of mitogen-activated protein kinase 1 (MAPK1) and inhibiting the p38/NF-κB pathway in LPS-induced HK-2 cells [ 58 ]. Additionally, miR-129-5p levels were decreased in septic AKI models in vivo and in vitro , and the anti-inflammatory effects of miR-129-5p were partly mediated by inhibiting Toll-like receptors (TLRs)/NF-κB signaling [ 59 ].…”