Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 11 min ago
Peer-reviewedCC BY-NC 4.0Zoological Research

Lipopolysaccharide-induced glycolytic reprogramming drives H3K18 lactylation-mediated inflammatory injury in buffalo mammary epithelial cells

  • Peng Xiao1,2,3,4
  • Xin-Ru Tian1,2,3
  • Jin-Chen Zhou2,3
  • Bo Zhang1
  • Meng-Qi Li1,2,3
  • Chun-Yan Yang2,3
  • Hai-Ying Zheng2,3
  • Meng-Jiao Chen4
  • Xiao-Gan Yang1
  • Jiang-Hua Shang2,3
  • Xing-Wei Liang1
4 affiliations
  1. 1Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science & Technology, Guangxi University, Nanning, Guangxi 530004, China
  2. 2Guangxi Key Laboratory of Buffalo Genetics, Reproduction and Breeding, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, Guangxi 530001, China
  3. 3Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Ministry of Agriculture and Rural Affairs, Nanning, Guangxi 530001, China
  4. 4College of Animal Science and Technology, Guangxi Vocational University of Agriculture, Nanning, Guangxi 530007, China
Read full textDOICite

Abstract

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.

Related

  1. Effects of Corydalis saxicola Bunting total alkaloids on lipopolysaccharide-induced inflammatory responses in human oral epithelial cells
    Yashi Qin, Yiyuan Lai, Jiaxuan Wu +5
    Biomedical reportsPeer-reviewedCC BY-NC-NDFull textPlant biologyEurope PMCPMC
  2. The metabolic crossfire hypothesis: glycolytic crosstalk between immune and epithelial cells in ulcerative colitis pathogenesis
    Liyao Wu, Jinyin Xiao, Chunhua Liu +2
    Frontiers in ImmunologyPeer-reviewedCC BY 4.0ImmunologyCrossref
  3. Forsythoside B attenuates neuropathic pain by suppressing USP7/HIF-1α-mediated microglial glycolytic reprogramming
    Z. Dai, H. Wang, Y. Yang
    bioRxivPreprintCC BYFull textNeurosciencebioRxiv
  4. Ginseng-derived extracellular vesicles alleviate ulcerative colitis by regulating macrophage glycolytic reprogramming and H3K18la-mediated epigenetic modification
    Yuzhe Zhang, Ruipeng Li, Yuan Yang +6
    Journal of Ginseng ResearchPeer-reviewedCC BY-NC-NDFull textGenetics & genomicsDOAJEurope PMCPMC
  5. Nitric Oxide Attenuates TGF-β-Induced Myofibroblast Differentiation Through Reversible Mitochondrial Bioenergetic Reprogramming Despite Compensatory Glycolytic Activation
    Madita Pflänzel, Juliana F. Bousch, Christoph V. Suschek +2
    CellsPeer-reviewedCC BY 4.0Cell biologyCrossref

Cite

BibTeXRIS
BibTeX
@article{xiao2026lipopolysaccharideinduced,
  title = {{Lipopolysaccharide-induced glycolytic reprogramming drives H3K18 lactylation-mediated inflammatory injury in buffalo mammary epithelial cells}},
  author = {Peng Xiao and Xin-Ru Tian and Jin-Chen Zhou and Bo Zhang and Meng-Qi Li and Chun-Yan Yang and Hai-Ying Zheng and Meng-Jiao Chen and Xiao-Gan Yang and Jiang-Hua Shang and Xing-Wei Liang},
  journal = {Zoological Research},
  year = {2026},
  month = sep,
  doi = {10.24272/j.issn.2095-8137.2025.523},
  url = {https://doi.org/10.24272/j.issn.2095-8137.2025.523},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Lipopolysaccharide-induced glycolytic reprogramming drives H3K18 lactylation-mediated inflammatory injury in buffalo mammary epithelial cells
AU  - Peng Xiao
AU  - Xin-Ru Tian
AU  - Jin-Chen Zhou
AU  - Bo Zhang
AU  - Meng-Qi Li
AU  - Chun-Yan Yang
AU  - Hai-Ying Zheng
AU  - Meng-Jiao Chen
AU  - Xiao-Gan Yang
AU  - Jiang-Hua Shang
AU  - Xing-Wei Liang
PY  - 2026
DA  - 2026/09/18
JO  - Zoological Research
DO  - 10.24272/j.issn.2095-8137.2025.523
UR  - https://doi.org/10.24272/j.issn.2095-8137.2025.523
AB  - 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.
SN  - 2095-8137
ER  -