Kisspeptin-10 通过下调 microRNA-1246 促进牛卵巢颗粒细胞孕激素的合成。

Kisspeptin-10 Promotes Progesterone Synthesis in Bovine Ovarian Granulosa Cells via Downregulation of microRNA-1246.

机构信息

Key Lab of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, China.

College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.

出版信息

Genes (Basel). 2022 Feb 3;13(2):298. doi: 10.3390/genes13020298.

The objective of this study was to clarify the effect of kisspeptin-10 (kp-10) on the synthesis of progesterone (P4) in bovine granulosa cells (BGCs) and its mechanisms via microRNA 1246 (miR-1246). According to the results, we found that treating with kp-10 for 24 h could increase P4 level, the mRNA expression of the steroidogenesis-related gene (StAR), free cholesterol content, and decrease miR-1246 expression in BGCs. Overexpression of miR-1246 significantly inhibited P4 synthesis, StAR mRNA expression, and free cholesterol content in BGCs, whereas underexpression of miR-1246 significantly reversed this effect in BGCs. Additionally, overexpression of miR-1246 counteracted the accelerative effect of kp-10 on P4 synthesis, StAR mRNA expression, and free cholesterol content in BGCs. Conversely, underexpression of miR-1246 enhanced the accelerative effect of kp-10 on P4 synthesis, StAR mRNA expression, and free cholesterol content in BGCs. Meanwhile, results of dual-luciferase reporter assays indicated that miR-1246 targeted the 3'UTR of StAR in BGCs. These results demonstrated that kp-10 induced P4 synthesis in BGCs by promoting free cholesterol transport via regulating expression of miR-1246/StAR.

本研究旨在阐明 kisspeptin-10（kp-10）通过 microRNA 1246（miR-1246）对牛颗粒细胞（BGCs）孕激素（P4）合成的影响及其机制。结果表明，kp-10 处理 24 h 可增加 BGCs 中 P4 水平、类固醇生成相关基因（StAR）的 mRNA 表达、游离胆固醇含量，并降低 miR-1246 表达。miR-1246 的过表达显著抑制 BGCs 中 P4 的合成、StAR mRNA 表达和游离胆固醇含量，而 miR-1246 的下调则显著逆转了 BGCs 中的这种作用。此外，miR-1246 的过表达抵消了 kp-10 对 BGCs 中 P4 合成、StAR mRNA 表达和游离胆固醇含量的加速作用。相反，miR-1246 的下调增强了 kp-10 对 BGCs 中 P4 合成、StAR mRNA 表达和游离胆固醇含量的加速作用。同时，双荧光素酶报告基因检测结果表明，miR-1246 靶向 BGCs 中的 StAR 3'UTR。这些结果表明，kp-10 通过调节 miR-1246/StAR 的表达促进游离胆固醇转运，诱导 BGCs 中 P4 的合成。