沉默HMGB1通过下调NF-κB信号来改善滋养细胞增殖侵袭及胰岛素抵抗和炎症反应

doi:10.3969/j.issn.1006-6233.2021.08.03

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Abstract Objective: To investigate the effects of silencing high mobility group 1 (HMGB1) on trophoblast proliferation, invasion, insulin resistance and inflammatory response in insulin resistance (IR). Methods: Human chorionic trophoblast cell line htr-8 was cultured and the expression of HMGB1 was silenced by shRNA transient transfection; the IR model of trophoblast cells was established in vitro, and the cells were divided into four groups: control group, insulin resistance group (IR group), IR+shRNA-NC group and IR+shrna-HMGB1 group. Western blot and immunofluorescence staining were used to detect the expression of HMGB1 in trophoblasts; CCK-8, Transwell and ELISA were used to detect the effects of HMGB1 silencing on the proliferation and invasion of trophoblasts and the expression of TNF-α, IL-1β and IL-6; Western blot was used to detect the effects of HMGB1 silencing on the phosphorylation of insulin sensitivity related proteins IRβ and PI3K, the expression of ISR-1, ISR-2, GLUT4 and GLUT1, and the phosphorylation levels of IκBα and p65 in NF-κB signaling pathway. Results: Compared with the control group, the glucose consumption, cell proliferation, invasion and protein GLUT-1 expression level of trophoblast in IR model were significantly decreased (P<0.05), the protein expression and fluorescence activity of HMGB1, the secretion levels of inflammatory factors TNF-α, IL-1β, IL-6, phosphorylation levels of proteins IRβ, PI3K, IκBα and p65, and the expressions of ISR-1, ISR-2 and GLUT4 were significantly increased (P<0.05). Compared with IR group, the glucose consumption, cell proliferation, invasion ability and GLUT-1 expression level of IR+shRNA-HMGB1 cells were significantly increased (P<0.05), protein expression and fluorescence activity of HMGB1, secretion levels of inflammatory factors TNF-α, IL-1β, IL-6, phosphorylation levels of proteins IRβ, PI3K, IκBα and p65, and expressions of ISR-1, ISR-2 and GLUT4 were significantly decreased (P<0.05). Conclusion: It found that HMGB1 expression level was significantly increased in the trophoblasts under IR condition. Silencing HMGB1 expression can promote the proliferation and invasion of trophoblasts through NF-κB signaling pathway, improve the sensitivity of trophoblasts to insulin, and reduce the secretion of pro-inflammatory factors.

Key words： HMGB1 Gestational diabetes mellitus Insulin resistance Trophoblast

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	GAO Yanyu
	LIN Juan
	WANG Qiong
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GAO Yanyu,LIN Juan,WANG Qiong, et al. Silencing HMGB1 Improves Trophoblast Cell Proliferation Invasion Insulin Resistance and Inflammation by Downregulating NF-κB Signaling[J]. HeBei Med, 2021, 27(8): 1244-1250.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2021.08.03 OR http://www.hbyxzzs.cn/EN/Y2021/V27/I8/1244

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