Article
作者: Choi, Young-Keun ; Choi, Dong-Hee ; Seo, Yun Jeong ; Choi, Jung Hyeon ; Kwon, Ha-Jeong ; Yoo, Hee Min ; Kim, Tae-Young ; Go, Jun ; Lee, Youngjin ; Kim, Yeon-Gu ; Kim, Byoung-Chan ; Jung, Kwang Bo ; Kim, Yong-Hoon ; Lee, In-Bok ; Kang, Eun-Jung ; Lee, Eun-Young ; Noh, Jung-Ran ; Seo, Seungwoo ; Park, Shinhye ; Lee, Dae-Hee ; Lee, Chul-Ho ; Kim, Kyoung-Shim ; Lee, Eun-Ji ; Jeong, Ji-Seon ; Kwon, Hyo-Jung ; Kim, Jae-Hoon ; Kim, Myung Hee ; Rhyoo, Moon-Young ; Kim, Young Eun ; Park, Sohee ; Kang, Ho Bum ; Huh, Yubin ; Kang, Dukjin ; Chang, Dong-Ho ; Hwang, Jung Hwan ; Son, Mi-Young ; Lee, Hana
AbstractAkkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.
