Department of Obstetrics and Gynecology, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China.
Mol Med Rep. 2022 May;25(5). doi: 10.3892/mmr.2022.12701. Epub 2022 Mar 29.
C1q/TNF‑α‑related protein 9 (CTRP9) is downregulated in gestational diabetes mellitus (GDM) and may exert a protective effect against GDM, although its mechanism of action is yet to be elucidated. To investigate the specific role of CTRP9 in GDM, the human placental trophoblast cell line HTR8/SVneo was treated with high glucose (HG) to simulate the environment of GDM . The effects of CTRP9 on the HTR8/SVneo cells and endoplasmic reticulum (ER) stress were analyzed before and after CTRP9 overexpression using reverse transcription‑quantitative PCR and western blotting. The results obtained demonstrated that CTRP9 alleviated ER stress in the trophoblast cell line. After treating with the ER‑stress inducer tunicamycin, cell viability was investigated by performing Cell Counting Kit‑8, TUNEL and western blotting assays, which revealed that CTRP9 increased the activity of HTR8/SVneo cells induced by HG through the alleviation of ER stress. Subsequently, ELISA and western blotting assay results demonstrated that CTRP9 inhibited HG‑induced inflammation of the HTR8/SVneo cells by the reduction in ER stress. Finally, the detection of reactive oxygen species, nitric oxide (NO) synthase and NO levels confirmed that CTRP9 inhibited the oxidative stress of HTR8/SVneo cells induced by HG through the reduction of ER stress. Collectively, the results of the present study suggested that CTRP9 may decrease trophoblast cell damage caused by HG through the suppression of ER stress, and therefore, CTRP9 may potentially be a therapeutic target in the treatment of GDM.
C1q/TNF-α-相关蛋白 9（CTRP9）在妊娠糖尿病（GDM）中下调，可能对 GDM 具有保护作用，但其作用机制尚不清楚。为了研究 CTRP9 在 GDM 中的具体作用，用人绒毛膜滋养层细胞系 HTR8/SVneo 处理高糖（HG）以模拟 GDM 环境。使用逆转录-定量 PCR 和 Western blot 分析 CTRP9 过表达前后对 HTR8/SVneo 细胞和内质网（ER）应激的影响。结果表明，CTRP9 减轻了滋养层细胞系中的 ER 应激。用 ER 应激诱导剂衣霉素处理后，通过 Cell Counting Kit-8、TUNEL 和 Western blot 测定法研究细胞活力，结果表明，CTRP9 通过减轻 ER 应激增加了 HG 诱导的 HTR8/SVneo 细胞的活性。随后，ELISA 和 Western blot 检测结果表明，CTRP9 通过减轻 ER 应激抑制了 HG 诱导的 HTR8/SVneo 细胞的炎症。最后，检测活性氧、一氧化氮（NO）合酶和 NO 水平证实，CTRP9 通过减轻 ER 应激抑制了 HG 诱导的 HTR8/SVneo 细胞的氧化应激。综上所述，本研究结果表明，CTRP9 可能通过抑制 ER 应激降低 HG 引起的滋养层细胞损伤，因此，CTRP9 可能是治疗 GDM 的潜在治疗靶点。
