1. Academic Validation
  2. Transcriptomics insights into glutamine on repairing of histamine-induced Yak rumen epithelial cells barrier damage in vitro

Transcriptomics insights into glutamine on repairing of histamine-induced Yak rumen epithelial cells barrier damage in vitro

  • BMC Genomics. 2025 Feb 25;26(1):195. doi: 10.1186/s12864-025-11383-6.
Xiaohong Zhang # 1 Rui Hu # 1 Zhisheng Wang 2 Junmei Wang 1 Ziqi Yue 1 Fali Wu 1 Wenjuan Zhou 1 Ali Mujtaba Shah 3
Affiliations

Affiliations

  • 1 Low Carbon Breeding Cattle and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agriculture University, Chengdu, 611130, China.
  • 2 Low Carbon Breeding Cattle and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agriculture University, Chengdu, 611130, China. zswangsicau@126.com.
  • 3 Key Laboratory of Animal Genetics, Breeding and Reproduction of Shanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.
  • # Contributed equally.
Abstract

Background: Glutamine (Gln) plays a pivotal role in maintaining the integrity of the rumen epithelial barrier in mammals. This study aimed to investigate the effects of Gln on histamine-induced barrier damage in yak rumen epithelial cells (YRECs).

Results: RT-qPCR analysis revealed a significant decrease in the mRNA expression of tight junction proteins (ZO-1, JAM-A, Claudin-1, and Claudin-4) following 24-hour exposure to 20 µM histamine (HIS group) (P < 0.05). In the subsequent experiment, YRECs were first treated with 20 µM histamine for 24 h, followed by 8 mM glutamine for 12 h (HG group). Gln treatment reversed the histamine-induced downregulation of both mRNA and protein levels of tight junction proteins and restored the distribution of ZO-1 at the cell membrane. Transcriptome analysis revealed that co-regulated differentially expressed genes were primarily involved in the mitogen-activated protein kinase (MAPK) signaling pathway and Apoptosis. These findings were further corroborated by RT-qPCR, Western blot, and flow cytometry analyses. To determine whether glutamine regulates cell barrier function through the p38 MAPK signaling pathway, 20 µM Skatole, a p38 MAPK Agonist, was introduced (SK group). The results showed a significant increase in the p-p38/p38 ratio and a marked decrease in the mRNA and protein expression of tight junction proteins in the SK group compared to the HG group (P < 0.05).

Conclusions: Glutamine mitigates histamine-induced barrier damage in YRECs through the p38 MAPK signaling pathway and Apoptosis regulation.

Keywords

Glutamine; Histamine; RNA-seq; Tight junction; Yak.

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