Overexpression of adrenomedullin (ADM) alleviates the senescence of human dental pulp stem cells by regulating the miR-152/CCNA2 pathway

Dou Wenxue; Xie Jiaye; Chen JiananZhou JiajunXu ZunyueWang ZhengZhu Qiang

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Overexpression of adrenomedullin (ADM) alleviates the senescence of human dental pulp stem cells by regulating the miR-152/CCNA2 pathway

机译：Overexpression of adrenomedullin (ADM) alleviates the senescence of human dental pulp stem cells by regulating the miR-152/CCNA2 pathway

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The limitation of human dental pulp stem cells (DPSCs), which have potential application value in regenerative medicine, is that they are prone to age in vitro. Studies have shown adrenomedullin (ADM) is believed to promote the proliferation of human DPSCs, but whether it can also affect aging remains to be investigated. A lentivirus vector was used to construct human DPSCs overexpressing ADM. Senescence tests were carried out on cells of the 7th and 15th passage. Transcriptome analysis was conducted to analyze microRNA expression regulation changes after human DPSCs overexpressed ADM. H2O2 induced the aging model of human DPSCs, and we examined the mechanism of recovery of aging through transfection experiments with miR-152 mimic, pCDH-CCNA2, and CCNA2 siRNA. Overexpression of ADM significantly upregulated the G2/M phase ratio of human DPSCs in natural passage culture (P = 0.001) and inhibited the expression of p53 (P = 0.014), P21 (WAF1) (P = 0.015), and P16 (INK4A) (P = 0.001). Decreased ROS accumulation was observed in human DPSCs during long-term natural passage (P = 0.022). Transcriptome analysis showed that miR-152 was significantly upregulated during human DPSC senescence (P = 0.001) and could induce cell senescence by directly targeting CCNA2. Transfection with miR-152 mimic significantly reversed the inhibitory effect of ADM overexpression on p53 (P = 0.006), P21 (WAF1) (P = 0.012), and P16 (INK4A) (P = 0.01) proteins in human DPSCs (H2O2-induced). In contrast, pCDH-CCNA2 weakened the effect of the miR-152 mimic, thus promoting cell proliferation and antiaging. ADM-overexpressing human DPSCs promote cell cycle progression and resist cellular senescence through CCNA2 expression promotion by inhibiting miR-152.

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《Cell cycle》 |2023年第5期|565-579|共15页
作者
Dou Wenxue; Xie Jiaye; Chen JiananZhou JiajunXu ZunyueWang ZhengZhu Qiang;
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作者单位

Naval Medical University,Naval Med Univ;

Dept Stomatol,Shanghai Jiao Tong Univ;

Dept Stomatol,Eastern Hepatobiliary Surg HospDept Stomatol,Shanghai Songjiang Dist Cent Hosp;

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正文语种英语
中图分类细胞生物学;
关键词
Dental pulp stem cells (DPSCs); adrenomedullin (ADM); miR-152; ccna2; OXIDATIVE STRESS; PROLIFERATION; EXPRESSION; APOPTOSIS;

Overexpression of adrenomedullin (ADM) alleviates the senescence of human dental pulp stem cells by regulating the miR-152/CCNA2 pathway

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