title: Downregulation of UBC9 promotes apoptosis of activated human LX-2 hepatic stellate cells by suppressing the canonical NF-κB signaling pathway.
abstract: UBC9, the only known E2-conjugating enzyme involved in SUMOylation, is a key regulator in fibrosis. However, the roles of UBC9 in liver fibrosis remain unclear. Therefore, in this study, we investigated the roles of UBC9 in HSC apoptosis and liver fibrogenesis. Our results showed that the UBC9 levels in activated LX-2 cells, HepG2 and SMMC-7721 were increased compared with LO2, and the expression of UBC9 in activated LX-2 cells, HepG2 and SMMC-7721 were no significant differences. The expression of UBC9 was effectively down-regulated by the UBC9-shRNA plasmid, and this effect was accompanied by the attenuated expression of the myofibroblast markers smooth muscle actin (α-SMA) and Collagen I. Downregulation of UBC9 also promotes activated HSCs apoptosis by up-regulating cell apoptosis-related proteins. Further, knockdown of UBC9 in activated HSCs inhibited cell viability and caused cell cycle arrest in the G2 phase. Moreover, knockdown of UBC9 suppressed the activation of NF-κB signaling pathways. In conclusion, these results demonstrated that down-regulation of UBC9 expression induced activated LX-2 cell apoptosis and promoted cells to return to a quiescent state by inhibiting the NF-κB signaling pathway. These results provide novel mechanistic insights for the anti-fibrotic effect of UBC9.
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Sufen
authors.identifier: http://orcid.org/0000-0001-6008-3432
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of interventional radiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Wuhua
authors.initials: W
authors.lastname: Guo
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D056945:Hep G2 Cells; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D024042:Collagen Type I; D016328:NF-kappa B; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9