Academic Journal
Lipopolysaccharide-induced glycolytic reprogramming drives H3K18 lactylation-mediated inflammatory injury in buffalo mammary epithelial cells.
| Τίτλος: | Lipopolysaccharide-induced glycolytic reprogramming drives H3K18 lactylation-mediated inflammatory injury in buffalo mammary epithelial cells. |
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| Συγγραφείς: | Xiao P; Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science & Technology, Guangxi University, Nanning, Guangxi 530004, China.; Guangxi Key Laboratory of Buffalo Genetics, Reproduction and Breeding, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, Guangxi 530001, China.; Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Ministry of Agriculture and Rural Affairs, Nanning, Guangxi 530001, China.; College of Animal Science and Technology, Guangxi Vocational University of Agriculture, Nanning, Guangxi 530007, China., Tian XR; Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science & Technology, Guangxi University, Nanning, Guangxi 530004, China.; Guangxi Key Laboratory of Buffalo Genetics, Reproduction and Breeding, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, Guangxi 530001, China.; Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Ministry of Agriculture and Rural Affairs, Nanning, Guangxi 530001, China., Zhou JC; Guangxi Key Laboratory of Buffalo Genetics, Reproduction and Breeding, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, Guangxi 530001, China.; Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Ministry of Agriculture and Rural Affairs, Nanning, Guangxi 530001, China., Zhang B; Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science & Technology, Guangxi University, Nanning, Guangxi 530004, China., Li MQ; Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science & Technology, Guangxi University, Nanning, Guangxi 530004, China.; Guangxi Key Laboratory of Buffalo Genetics, Reproduction and Breeding, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, Guangxi 530001, China.; Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Ministry of Agriculture and Rural Affairs, Nanning, Guangxi 530001, China., Yang CY; Guangxi Key Laboratory of Buffalo Genetics, Reproduction and Breeding, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, Guangxi 530001, China.; Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Ministry of Agriculture and Rural Affairs, Nanning, Guangxi 530001, China., Zheng HY; Guangxi Key Laboratory of Buffalo Genetics, Reproduction and Breeding, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, Guangxi 530001, China.; Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Ministry of Agriculture and Rural Affairs, Nanning, Guangxi 530001, China., Chen MJ; College of Animal Science and Technology, Guangxi Vocational University of Agriculture, Nanning, Guangxi 530007, China., Yang XG; Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science & Technology, Guangxi University, Nanning, Guangxi 530004, China., Shang JH; Guangxi Key Laboratory of Buffalo Genetics, Reproduction and Breeding, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, Guangxi 530001, China.; Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Ministry of Agriculture and Rural Affairs, Nanning, Guangxi 530001, China. E-mail: jh_shang@163.com., Liang XW; Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science & Technology, Guangxi University, Nanning, Guangxi 530004, China. E-mail: xwliang@gxu.edu.cn. |
| Πηγή: | Zoological research [Zool Res] 2026 Sep 18; Vol. 47 (5), pp. 1780-1792. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Science Press Country of Publication: China NLM ID: 101697192 Publication Model: Print Cited Medium: Internet ISSN: 2095-8137 (Print) Linking ISSN: 20958137 NLM ISO Abbreviation: Zool Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Beijing, China : Science Press, 2016- |
| Ιατρικοί όροι (MeSH): | Lipopolysaccharides*/toxicity , Epithelial Cells*/drug effects , Epithelial Cells*/metabolism , Mastitis*/veterinary , Mastitis*/chemically induced , Mastitis*/metabolism , Mammary Glands, Animal*/cytology , Mammary Glands, Animal*/drug effects , Inflammation*/chemically induced , Inflammation*/veterinary , Inflammation*/metabolism , Glycolysis*/drug effects , Histones*/metabolism , Histones*/genetics , Buffaloes*, Gene Expression Regulation/drug effects ; Animals ; Female ; Mice ; Apoptosis |
| Περίληψη: | Buffalo mastitis impairs milk production and quality, yet the underlying epigenetic mechanisms remain unclear. While LPS-induced glycolytic activation and lactate accumulation contribute to inflammation, their role in histone lactylation-mediated injury is unexplored. Our results revealed that mammary tissues from buffalo with clinical mastitis exhibited elevated LPS levels, upregulation of inflammatory markers, enhanced apoptosis, and markedly higher levels of lactate, Pankla, and H3K18la compared to healthy controls. Similarly, an LPS-induced mouse mastitis model recapitulated the inflammatory and apoptotic features observed in buffalo tissues, confirming LPS as a key driver of mammary tissue injury. In vitro, LPS treatment of buffalo mammary epithelial cells (BuMECs) upregulated proinflammatory and proapoptotic markers while downregulating antiapoptotic genes. RNA-seq and western blot analyses further revealed that LPS enhanced the expression and activity of key glycolytic enzymes, such as HK2, PKM2, PDK1, and LDHA, thereby promoting glycolytic flux, increasing lactate production, and elevating Pankla and H3K18la levels. CUT&Tag analysis suggested that H3K18la may facilitate the recruitment of transcriptional regulators, such as DDIT3, NF-κB1, and CEBPD, potentially linking lactylation to the activation of inflammatory and apoptotic pathways. Importantly, inhibition of HK2 reduced lactate accumulation, decreased H3K18la levels, and substantially attenuated inflammatory injury in BuMECs. Together, these findings identify the HK2-lactate-H3K18la axis as a central mechanism in LPS-induced inflammatory injury in BuMECs and underscore its potential as a therapeutic target for alleviating mastitis and enhancing mammary health in dairy buffalo. |
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| Contributed Indexing: | Keywords: Buffalo mammary epithelial cells; Glycolysis; Histone lactylation; Lipopolysaccharide; Mastitis Local Abstract: [Publisher, Chinese] 乳房炎会导致水牛产奶量和奶品质下降，但其潜在的表观遗传机制尚不清楚。虽然脂多糖（Lipopolysaccharide，LPS）诱导的糖酵解激活和乳酸积累会导致炎症，但在组蛋白乳酸化介导的炎症损伤中的作用机制尚不明确。本研究结果表明，与健康对照组相比患有临床乳腺炎的水牛乳腺组织中LPS水平升高，炎症标志物表达上调，细胞凋亡增强，乳酸、Pankla和H3K18la的水平也显著升高。同样，LPS诱导的小鼠乳房炎模型重现了水牛组织中观察到的炎症和凋亡特征，证实了LPS是乳腺组织损伤的关键驱动因素。体外实验表明，LPS处理水牛乳腺上皮细胞（Buffalo mammary epithelial cells，BuMECs）可上调促炎和促凋亡标志物，同时下调抗凋亡基因。转录组测序和蛋白质免疫印迹分析进一步揭示，LPS增强了 HK2、PKM2、PDK1和 LDHA糖酵解酶的表达活性，从而促进糖酵解通量，增加乳酸生成，并提高Pankla和H3K18la的水平。CUT&Tag分析表明，H3K18la促进 DDIT3、NF-κB1和 CEBPD转录调节因子的募集，从而可能将乳酸化与炎症和凋亡通路的激活联系起来。重要的是， HK2抑制剂可减少乳酸积累，降低H3K18la水平，并显著减轻BuMECs中的炎症损伤。综上所述，本研究表明HK2-乳酸-H3K18la轴是LPS诱导BuMECs炎症损伤的核心作用机制，其作为治疗靶点在缓解水牛乳房炎和改善乳腺健康方面具有潜在价值。. |
| Substance Nomenclature: | 0 (Lipopolysaccharides) 0 (Histones) |
| Entry Date(s): | Date Created: 20260913 Date Completed: 20260913 Latest Revision: 20260913 |
| Update Code: | 20260914 |
| DOI: | 10.24272/j.issn.2095-8137.2025.523 |
| PMID: | 42733043 |
| Βάση Δεδομένων: | MEDLINE |
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