Ubiquitin fold modifier 1 activates NF-κB pathway by down-regulating LZAP expression in the macrophage of diabetic mouse model. Issue 1 (2nd January 2020)

• Record Type: Journal Article
• Authors: Hu, Xiaolei; Zhang, Hengyan; Song, Yuan; Zhuang, Langen; Yang, Qingqing; Pan, Minglin; Chen, Fengling
• Is Part Of: Bioscience reports. Volume 40:Issue 1(2020)
• Publication Date: 2020-01-02
• Subjects: Diabetes mellitus -- LZAP -- NF-κB -- Ubiquitin-fold modifer 1; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20191672
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract: Inflammatory response is closely related with the development of many serious health problems worldwide including diabetes mellitus (DM). Ubiquitin-fold modifer 1 (Ufm1) is a newly discovered ubiquitin-like protein, while its function remains poorly investigated, especially in inflammatory response and DM. In the present study, we analyzed the role of Ufm1 on inflammatory response in DM, and found that the proinflammatory cytokine levels (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β) and Ufm1 expression were highly increased both in the peritoneal macrophages of db/db mice and Raw264.7 cells induced by lipopolysaccharide (LPS). Western blot and luciferase reporter assay showed that NF-κB pathway was obviously activated in macrophages and the expression of LZAP, an inhibitor of NF-κB pathway, was down-regulated. With the LZAP knockdown plasmid and activation plasmid, we demonstrated that NF-κB/p65 activation was inhibited by LZAP in macrophages. The interaction of Ufm1 and LZAP was further proved with co-immunoprecipitation assay in HEK293 and Raw264.7 cells. The LZAP expression was also related with the presence of Ufm1 demonstrated by Ufm1 knockdown plasmid and activation plasmid. Besides that, we finally proved that the expression and activation of Ufm1 induced by LPS were regulated by JNK/ATF2 and JNK/c-Jun pathway with the use of SP600125. In conclusion, the present study demonstrated that Ufm 1 could activate NF-κB pathway by down-regulating LZAP in macrophage of diabetes, and its expression and activation were regulated by JNK/ATF2 and c-Jun pathway.