Inhibition of miR‐181a attenuates sepsis‐induced inflammation and apoptosis by activating Nrf2 and inhibiting NF‐κB pathways via targeting SIRT1

Abstract

Sepsis is caused by microbial infection with high mortality worldwide, and characterized by multiple organ dysfunction and systemic inflammatory response. Previous study shows that miR‐181a level is increased during sepsis; however, the mechanism is still unknown. Therefore, to identify the role of miR‐181a, lipopolysaccharide (LPS) was used to stimulate mouse peritoneal macrophages. The expressions of miR‐181a and SIRT1 were identified by QRT‐PCR, the levels of SIRT1, Nrf2, p‐P65, Bcl‐2 and Bax were detected by western blotting, the inflammatory cytokines TNF‐α, IL‐6 and IL‐1β were detected by ELISA, and the apoptosis was measured by flow cytometry. Bioinformatics and dual luciferase assay were used to unveil the binding sites and the targeted regulatory relationship of miR‐181a and SIRT1. LPS induced the upregulation of miR‐181a, downregulation of SIRT1 and a strong inflammatory response. In addition, LPS stimulation inhibited the expression of Nrf2 and activated the NF‐κB pathway. Moreover, the inhibition of miR‐181a attenuated inflammatory response and apoptosis during LPS stimulation, which was implemented by up‐regulating the expression of its target SIRT1. More fully, downregulation of SIRT1 by short hairpin interference resulted in a decreased expression of Nrf2, increased expression of p‐P65 and proinflammatory cytokines, and intensive apoptosis. Downregulation of miR‐181a could promote the expression of its target SIRT1, and then, attenuate inflammatory response and apoptosis via Nrf2 and NF‐κB signaling pathways during LPS treatment. miR‐181a can be a potential target of controlling the inflammatory response during sepsis and has important clinical significance for the treatment and rehabilitation of septic patients.

Formononetin ameliorates IL‑13‑induced inflammation and mucus formation in human nasal epithelial cells by activating the SIRT1/Nrf2 signaling pathway

“…SIRT1 is a well-known regulator of chronic inflammatory responses, which has been investigated in the context of the alleviation of asthma as well as allergic rhinitis ( 15 , 59 ). Wu et al ( 60 ) found that SIRT1 activation upregulated Nrf2 expression and inhibited the NF-κB signaling pathway to relieve sepsis-induced inflammation and apoptosis. Furthermore, it was demonstrated in a previous study that formononetin served as a SIRT1 activator and improved diabetic neuropathy ( 61 ).…”

The molecular activity of cannabidiol in the regulation of Nrf2 system interacting with NF-κB pathway under oxidative stress

“…Moreover, miRNAs have critical impacts on the regulation of gene expression and associated biological processes such as proliferation, apoptosis, tumorigenesis [ 92 ], and even cell-cell communication (as suggested via vesicle-free extracellular miRNAs) [ 93 ]. Considering this regulatory role of miRNAs, and other transcription regulatory molecules involved in the Nrf2 pathway (such as miR-365-1, miR-193b, miR-29-b1, miR-93, miR-153, miR-27-a, miR-142–5p [ 94 ], miR-21 [ 95 ], miR-144 [ 96 ], miR-125b [ 97 ], miR-181a [ 98 ], hsa_circ_0005915 [ 99 ], miR-145–5p, miR-104–5p, miR-200a [ 100 ]) may be important to evaluate CBD action which may have a great potential to change Nrf2 activity.…”

Sevoflurane ameliorates LPS-induced inflammatory injury of HK-2 cells through Sirtuin1/NF-κB pathway

“…35 Our results showed that SEV up-regulated IκBα expression and down-regulated the expressions of p-p65 and acetyl-p53 in LPS-induced HK-2 cells, indicating activating the NF-κB signaling pathway 46 and sepsis-induced inflammation and apoptosis could be alleviated by inhibiting the NF-κB pathway via targeting SIRT1. 47 Therefore, we speculated that SEV suppressed the apoptosis of LPSinduced HK-2 cells by promoting the SIRT1 expression and inactivating the NF-κB signaling pathway.…”