LIN28A blocks the EndMT process of high glucose-induced HRMECs by stabilizing SIRT6 mRNA.

IF 3 3区医学

Journal of Diabetes Investigation Pub Date : 2026-05-01 Epub Date: 2026-03-07 DOI:10.1111/jdi.70284

Xueying Wang, Zixu Huang, Xiaohui Kuang, Yali Nan, Zhiwen Zhang, Zongming Song

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引用次数: 0

Abstract

Background: Diabetic retinopathy (DR) is a microvascular condition resulting from microangiopathy, causing gradual retinal damage and potential blindness. Endothelial-mesenchymal transition (EndMT) serves an important function in DR development. Exploring the molecular mechanism of EndMT in DR is needed.

Methods: Human retinal microvascular endothelial cells (HRMECs) were incubated with high glucose (HG) to induce an in vitro DR model. Lentivirus and small-interfering RNAs were used to construct SIRT6 and LIN28A overexpression or knockdown in HRMECs, respectively. AMPK inhibitor, compound C, was used to block AMPK signaling in HRMECs. α-SMA and PECAM1 levels were identified using immunofluorescence. CCK8 and transwell were used to detect cell viability and migration, respectively. The mRNA stability of SIRT6 was analyzed after HRMECs were exposed to actinomycin D. RNA immunoprecipitation was applied to verify the binding relationship between LIN28A and SIRT6 mRNA in HRMECs.

Results: In HG-induced HRMECs, the cells undergo the EndMT process, and SIRT6 levels are downregulated. HG treatment reduced the level of p-AMPK in HRMECs, and compound C reversed the inhibition of SIRT6 overexpression on EndMT in HG-induced HRMECs. By binding to SIRT6 mRNA, LIN28A could enhance SIRT6 mRNA stability. Additionally, LIN28A overexpression inhibited EndMT in HG-induced HRMECs, which was reversed by SIRT6 knockdown.

Conclusion: The stabilization of SIRT6 mRNA by LIN28A activated AMPK signaling, inhibiting the EndMT process in HRMECs caused by HG.

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LIN28A通过稳定SIRT6 mRNA阻断高糖诱导的hrmec的EndMT过程。

背景：糖尿病视网膜病变（DR）是一种由微血管病变引起的微血管疾病，可导致视网膜逐渐损伤和潜在失明。内皮-间充质转化（EndMT）在DR的发展中起着重要的作用。研究EndMT在DR中的分子机制是很有必要的。方法：将人视网膜微血管内皮细胞（HRMECs）与高糖（HG）培养，建立体外DR模型。使用慢病毒和小干扰rna分别构建hrmes中SIRT6和LIN28A过表达或低表达。AMPK抑制剂化合物C用于阻断hrmes中的AMPK信号传导。免疫荧光法检测α-SMA和PECAM1水平。CCK8和transwell分别检测细胞活力和迁移。分析放线菌素d作用于hrmes后SIRT6 mRNA的稳定性，采用RNA免疫沉淀法验证hrmes中LIN28A与SIRT6 mRNA结合关系。结果：hg诱导的hrmes细胞发生EndMT过程，SIRT6水平下调。HG处理降低了HRMECs中p-AMPK的水平，化合物C逆转了HG诱导的HRMECs中SIRT6过表达对EndMT的抑制。LIN28A通过与SIRT6 mRNA结合，增强SIRT6 mRNA的稳定性。此外，在hg诱导的hrmes中，LIN28A过表达抑制了EndMT，而SIRT6敲低可以逆转这一现象。结论：LIN28A稳定SIRT6 mRNA激活AMPK信号，抑制HG所致hrmes的EndMT过程。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Diabetes Investigation Medicine-Internal Medicine

自引率

9.40%

发文量

218

期刊介绍： Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).