Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, PR China.
School of Physical Education and International Equestrianism, Wuhan Business University, Wuhan, PR China.
Theriogenology. 2024 Jan 15;214:307-313. doi: 10.1016/j.theriogenology.2023.11.003. Epub 2023 Nov 7.
Endometritis is one of the important reasons for the low fecundity of dairy cows, which has brought huge economic losses to the dairy industry. Emerging evidence suggests that miR-92b is a novel therapeutic molecule that plays a crucial role in many inflammatory diseases. However, its mechanism in lipoteichoic acid (LTA) induced endometritis remains unclear. In the present study, we explored the mechanism of miR-92b on LTA-induced endometritis in vivo and in vitro. The result displayed that the expression of miR-92b was reduced in LTA induced mouse endometritis and bovine endometrial epithelial cell lines (BEND). Overexpression miR-92b significantly alleviated mouse uterine injury and reduced the protein levels of TNF-α, IL-1β and the MPO activity. The reporter assay of luciferase showed that miR-92b directly targeted the transmembrane receptor Frizzled-10 (FZD10), a transmembrane-type Wnt receptor. Molecular experiments were further performed to explore the mechanism of miR-92b in protecting LTA induced endometritis. The results of in vitro suggested that miR-92b mimic decreased the protein levels of Wnt3a and β-catenin in LTA stimulated BEND, which were abolished by overexpression of FZD10. As expected, miR-92b mimic decreased the expression levels of TNF-α and IL-1β, while overexpression of FZD10 promoted the production of these pro-inflammatory cytokines. Collectively, the above findings indicated that miR-92b might be an effective strategy for treatment of LTA induced endometritis.
子宫内膜炎是奶牛低生育率的重要原因之一，给奶牛养殖业带来了巨大的经济损失。新出现的证据表明，miR-92b 是一种新型治疗分子，在许多炎症性疾病中发挥着关键作用。然而，其在脂磷壁酸（LTA）诱导的子宫内膜炎中的机制尚不清楚。在本研究中，我们探讨了 miR-92b 在 LTA 诱导的子宫内膜炎体内和体外的作用机制。结果显示，LTA 诱导的小鼠子宫内膜炎和牛子宫内膜上皮细胞系（BEND）中 miR-92b 的表达降低。过表达 miR-92b 可显著减轻小鼠子宫损伤，降低 TNF-α、IL-1β 和 MPO 活性的蛋白水平。荧光素酶报告基因检测显示，miR-92b 可直接靶向跨膜受体卷曲蛋白 10（FZD10），一种跨膜型 Wnt 受体。进一步进行分子实验以探讨 miR-92b 保护 LTA 诱导的子宫内膜炎的机制。体外实验结果表明，miR-92b 模拟物降低了 LTA 刺激的 BEND 中 Wnt3a 和 β-连环蛋白的蛋白水平，而过表达 FZD10 则消除了这一作用。预期的是，miR-92b 模拟物降低了 TNF-α 和 IL-1β 的表达水平，而过表达 FZD10 则促进了这些促炎细胞因子的产生。综上所述，这些发现表明 miR-92b 可能是治疗 LTA 诱导的子宫内膜炎的有效策略。
