Department of Clinical Nutrition, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiangxi Road, Guangzhou, Guangdong, 510120, People's Republic of China.
Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiangxi Road, Guangzhou, Guangdong, 510120, People's Republic of China, China.
Endocr Metab Immune Disord Drug Targets. 2023;23(9):1186-1200. doi: 10.2174/1871530323666230206121715.
The RAS system is involved in the regulation of islet function, but its regulation remains unclear.
This study investigates the role of an islet-specific miR-375 in the effect of RAS system on islet β-cells.
miR-375 mimics and inhibitors were transfected into insulin-secreting MIN6 cells in the presence or absence of RAS component.
Compared to control, in Ang II-treated MIN6 cells, miR-375 mimic transfection results in a decrement in cell viability and Akt-Ser levels (0.739±0.05 vs. 0.883±0.06 and 0.40±0.04 vs. 0.79±0.04, respectively), while the opposite occurred in miR-375 inhibitor-transfected cells (1.032±0.11 vs. 0.883±0.06 and 0.98±0.05 vs. 0.79±0.04, respectively, P<0.05). Mechanistically, transfection of miR- 375 mimics into Ang II-treated MIN6 cells significantly reduced the expression of Mapkap1 protein (0.97±0.15 vs. 0.63±0.06, P<0.05); while miR-375 inhibitor-transfected cells elevated Mapkap1 expression level (0.35±0.11 vs. 0.90±0.05, P<0.05), without changes in mRNA expression. Transfection of miR-375 specific inhibitors TSB-Mapkap1 could elevate Mapkap1 (1.62±0.02 vs. 0.68±0.01, P<0.05), while inhibition of Mapkap1 could significantly reduce the level of Akt-Ser473 phosphorylation (0.60±0.14 vs. 1.80±0.27, P<0.05).
The effects of Ang II on mouse islet β cells were mediated by miR-375 through miR- 375/Mapkap 1 axis. This targeted regulation may occur by affecting Akt phosphorylation of β cells. These results may provide new ideas and a scientific basis for further development of miRNA-targeted islet protection measures.
RAS 系统参与胰岛功能的调节，但具体的调节机制尚不清楚。
本研究旨在探讨胰岛特异性 miR-375 在 RAS 系统对胰岛β细胞作用中的功能。
在存在或不存在 RAS 成分的情况下，将 miR-375 模拟物和抑制剂转染至胰岛素分泌 MIN6 细胞中。
与对照组相比，在 Ang II 处理的 MIN6 细胞中，miR-375 模拟物转染导致细胞活力和 Akt-Ser 水平降低（分别为 0.739±0.05 与 0.883±0.06 和 0.40±0.04 与 0.79±0.04），而 miR-375 抑制剂转染的细胞则相反（分别为 1.032±0.11 与 0.883±0.06 和 0.98±0.05 与 0.79±0.04，P<0.05）。在机制上，miR-375 模拟物转染 Ang II 处理的 MIN6 细胞可显著降低 Mapkap1 蛋白的表达（0.97±0.15 与 0.63±0.06，P<0.05）；而 miR-375 抑制剂转染的细胞则升高了 Mapkap1 表达水平（0.35±0.11 与 0.90±0.05，P<0.05），但 mRNA 表达无变化。转染 miR-375 特异性抑制剂 TSB-Mapkap1 可升高 Mapkap1（1.62±0.02 与 0.68±0.01，P<0.05），而抑制 Mapkap1 可显著降低 Akt-Ser473 磷酸化水平（0.60±0.14 与 1.80±0.27，P<0.05）。
Ang II 对胰岛β细胞的作用是通过 miR-375 通过 miR-375/Mapkap1 轴介导的。这种靶向调节可能通过影响β细胞的 Akt 磷酸化来发生。这些结果可能为进一步开发 miRNA 靶向胰岛保护措施提供新的思路和科学依据。
