1. 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
- Author
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Hongbin Mou, Bo Gao, Gang Zhou, Changhua Liu, Xiaolan Xu, and Haixia Wang
- Subjects
Lipopolysaccharides ,Male ,endocrine system ,p38 mitogen-activated protein kinases ,Apoptosis ,Bioengineering ,p38 Mitogen-Activated Protein Kinases ,Applied Microbiology and Biotechnology ,Cell Line ,Rats, Sprague-Dawley ,MAPK1 ,chemistry.chemical_compound ,p38/nf-κB ,Sepsis ,Animals ,Humans ,Medicine ,Gene Silencing ,Protein kinase A ,Inflammation ,Mitogen-Activated Protein Kinase 1 ,Gene knockdown ,Base Sequence ,biology ,business.industry ,NF-kappa B ,Acute kidney injury ,NF-κB ,ceRNA ,General Medicine ,Acute Kidney Injury ,medicine.disease ,Up-Regulation ,Antisense RNA ,MicroRNAs ,chemistry ,Potassium Channels, Voltage-Gated ,Mitogen-activated protein kinase ,Cancer research ,biology.protein ,KCNQ1OT ,MiR-212 ,business ,TP248.13-248.65 ,Signal Transduction ,Research Article ,Research Paper ,Biotechnology - 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.
- Published
- 2021