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LncRNA Gm26917 promotes macrophage differentiation by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury

ABSTRACT: Our studies demonstrated that Gm26917 localized in the cytoplasm of hepatic macrophages and globally regulated expressions of inflammatory genes and differentiation of macrophages. In vivo study showed that lentivirus-mediated gene silencing of Gm26917 attenuated liver inflammation and protected mice from LPS-induced ALI. Furthermore, mechanistic study showed that 3’- truncation of Gm26917 interacts with N-terminus of Annexin A1, a negative regulator of NF-κB signaling pathway. We also found that Gm26917 knockdown suppressed NF-κB activity by decreasing the ubiquitination of Annexin A1 and its interaction with NEMO. Besides, expression of Gm26917 in inflammatory macrophage was regulated by transcription factor forkhead box M1 (FOXM1). LPS treatment could dramatically increase the binding of FOXM1 to the promoter region of Gm26917 in macrophages. In sum, our findings suggest that lncRNA Gm26917 silencing protected against LPS-induced liver injury by regulating TLR4/NF-κB signaling pathway in macrophages.

ORGANISM(S): Mus musculus

PROVIDER: GSE185716 | GEO | 2022/09/01

REPOSITORIES: GEO

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