2. Academic Validation
  3. Kynurenine promotes porcine intestinal epithelial cell proliferation by activating the AHR-MST1-YAP1 axis

Kynurenine promotes porcine intestinal epithelial cell proliferation by activating the AHR-MST1-YAP1 axis

  • J Anim Sci Biotechnol. 2026 Mar 17;17(1):50. doi: 10.1186/s40104-026-01368-0.
Zhenguo Hu # 1 2,  Lanmei Yin # 3,  Qianqian Wang 3,  Junhao Deng 1,  Xiaofeng Zhu 1,  Huansheng Yang 3,  Pengpeng Zhang 4,  Yulong Yin 5 6 7,  Xiongzhuo Tang 8 9
Affiliations

Affiliations

  • 1 Animal Nutritional Genome and Germplasm Innovation Research Center, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China.
  • 2 Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Science, Changsha, Hunan, 410125, China.
  • 3 Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
  • 4 Transplantation Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
  • 5 Animal Nutritional Genome and Germplasm Innovation Research Center, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China. [email protected].
  • 6 Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Science, Changsha, Hunan, 410125, China. [email protected].
  • 7 Yuelushan Laboratory, Changsha, Hunan, 410128, China. [email protected].
  • 8 Animal Nutritional Genome and Germplasm Innovation Research Center, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China. [email protected].
  • 9 Yuelushan Laboratory, Changsha, Hunan, 410128, China. [email protected].
  • # Contributed equally.
PMID: 41845541 DOI: 10.1186/s40104-026-01368-0
Abstract

Background: The objective of this study was to investigate the effect of L-tryptophan (L-Trp) and its metabolite kynurenine (Kyn) on the regulation of porcine intestinal epithelial cell proliferation.

Results: Dietary supplementation of L-Trp significantly increased villus height and decreased crypt depth in the jejunum and ileum of weaned pigs. mRNA Sequencing data and qPCR analysis found that L-Trp activated the expression of cell proliferative genes and the AHR (Aryl Hydrocarbon Receptor)-MST1 (mammalian STE20-like kinase 1)-YAP1 (Yes-associated protein 1) axis in the ileum. Further in vitro analysis revealed that L-Trp treatment significantly enhanced cell proliferation of intestinal porcine epithelial cells-jejunum 2 (IPEC-J2) cells by activating the MST1-YAP1 signaling pathway. Further targeted metabolomics analysis identified Kyn as the core Trp metabolite involved in promoting IPEC-J2 cell proliferation. Mechanistically, Kyn interacted with AHR, which in turn bound to the upstream promote region of MST1 to initiate the transcription of downstream target gene YAP1 to activate intestinal epithelial cell proliferation. Furthermore, porcine intestinal Organoid model also demonstrated that Kyn promoted intestinal organoid-budding efficiency and intestinal stem cell proliferation. Importantly, by using the AHR- or YAP1-specific inhibitors, the data confirmed that the Kyn-induced intestinal epithelial cell proliferation in IPEC-J2 cells and intestinal organoids was dependent on the activation of the AHR-MST1-YAP1 axis.

Conclusions: Together, this study has revealed a regulatory mechanism of Trp metabolism-derived Kyn in promoting porcine intestinal epithelial cell proliferation, offering insights into the connection between nutrient metabolism and intestinal epithelial homeostasis.

Keywords

Aryl hydrocarbon receptor; Intestinal epithelial cell proliferation; Kynurenine; Tryptophan metabolism.

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