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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\n                      <jats:italic>MST1<\/jats:italic>\n                      to initiate the transcription of downstream target gene\n                      <jats:italic>YAP1<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40104-026-01368-0","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T10:49:40Z","timestamp":1773744580000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Kynurenine promotes porcine intestinal epithelial cell proliferation by activating the AHR-MST1-YAP1 axis"],"prefix":"10.1186","volume":"17","author":[{"given":"Zhenguo","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanmei","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhao","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huansheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengpeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9875-8829","authenticated-orcid":false,"given":"Xiongzhuo","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"1368_CR1","doi-asserted-by":"publisher","unstructured":"Matsumura S, Kurashima Y, Murasaki S, Morimoto M, Arai F, Saito Y, et al. 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