HADHA promotes apoptosis and inflammatory response in bovine endometrial epithelial cells by regulating transcription and metabolism

文献类型： 外文期刊

第一作者： Ji, Guoshang

作者： Ji, Guoshang;Feng, Xue;Hu, Chunli;Zhang, Junxing;Sheng, Hui;Na, Rina;Li, Fen;Wang, Yachun;Ma, Yanfen;Cai, Bei;Ma, Yun;Zhang, Junxing;Sheng, Hui;Wang, Yachun

作者机构：

关键词： HADHA; Bovine endometrial epithelial cells; Inflammation; Multiomics

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.5； 五年影响因子：8.7 ）

ISSN： 0141-8130

年卷期： 2025 年 304 卷

页码：

收录情况： SCI

摘要： Endometritis in dairy cows significantly impacts their reproductive performance. However, its underlying mechanisms remain unclear. Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit-alpha (HADHA) is known to regulate the occurrence of various diseases, but its role in bovine endometritis is poorly understood. In the present study, an in vitro bovine endometrial epithelial cells (BEECs) inflammation model was constructed to explore the effects of HADHA on inflammation, proliferation, and apoptosis. Functional analyses based on HADHA interference and overexpression revealed that it positively regulated the expression of IL-6, IL8, and IL-1 beta in lipopolysaccharide (LPS)-induced BEECs, enhancing reactive oxygen species (ROS) production and promoting inflammation. Concurrently, HADHA decreased the expression of PCNA, CDK2, and CDK4, inhibited mitotic transition of BEECs from S to G2 phase, and negatively regulated BEEC proliferation. It also increased BAX and Caspase-3 expression while decreasing BCL2 expression, hence promoting BEECs apoptosis. Transcriptomic and metabolomic analyses indicated that HADHA modulated inflammation in BEECs by affecting pathways such as the TGF-beta signaling pathway, fatty acid metabolism, and p53 signaling. These findings provide novel insights into HADHA's role in bovine endometritis and reveal future research directions on its regulatory mechanisms.

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