FOXM1通过靶向上调PHB2的转录改善线粒体功能障碍保护脂多糖诱导的肾小管上皮细胞损伤

doi:10.3969/j.issn.1006-6233.2022.03.04

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Abstract Objective: To explore the role of FOXM1 in lipopolysaccharide (LPS)-induced renal tubular epithelial cell injury and its possible mechanism. Methods: Human renal tubular epithelial cells HK-2 were cultured in vitro. QRT-PCR and Western blot were used to detect the expression of FOXM1 and PHB2; CCK-8 was used to detect cell viability; flow cytometry was used to detect cell apoptosis; JC-1 staining was used to detect the mitochondrial membrane potential; the reagent kit was used to detect cellular ATP content; the luciferase reporter experiment and ChIP-PCR experiment were used to detect the regulatory effect of FOXM1 on the PHB2 promoter. Results: Compared with the control group, the expression of FOXM1 and PHB2, cell viability, red/green fluorescence intensity ratio and ATP content in the cells of the LPS group were significantly reduced (P<0.05), and the apoptosis rate was significantly increased (P<0.05); compared with the LPS group, there was no significant difference in FOXM1 and PHB2 expression, cell viability, red/green fluorescence intensity ratio, ATP content and apoptosis rate in the cells of the LPS+oe-NC group (P>0.05); compared with the LPS+oe-NC group, the expression of FOXM1 and PHB2, cell viability, red/green fluorescence intensity ratio and ATP content in the cells of the LPS+oe-FOXM1 group were significantly increased (P<0.05), and the apoptosis rate was significantly reduced (P<0.05). FOXM1 targeted the PHB2 promoter region. Compared with the LPS+oe-NC+sh-NC group, the FOXM1 and PHB2 protein expression, cell viability, red/green fluorescence intensity ratio and ATP content in the cells of the LPS+oe-FOXM1+sh-NC group were significantly increased (P<0.05), the cell apoptosis rate was significantly reduced (P＜0.05); compared with the LPS+oe-NC+sh-NC group, the expression of PHB2 protein, cell viability, red/green fluorescence intensity ratio and ATP content in the cells of the LPS+oe-NC+sh-PHB2 group were significantly reduced (P＜0.05), the apoptosis rate was significantly increased (P<0.05), and the difference in FOXM1 protein expression was not statistically significant (P>0.05); sh-PHB2 can partially reverse the effect of oe-FOXM1 on HK-2 cells treated with LPS. Conclusion: FOXM1 promotes PHB2 expression by targeting the PHB2 promoter region to improve mitochondrial dysfunction, and then to inhibit LPS-induced renal tubular epithelial cell damage.

Key words： Renal tubular epithelial cells Lipopolysaccharide Forkhead box M1 Prohibitin 2 Mitochondria

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2022.03.04 OR http://www.hbyxzzs.cn/EN/Y2022/V28/I3/368

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