| Autor: |
Maria R. Encarnacion-Garcia, Raul De la Torre-Baez, Maria A. Hernandez-Cueto, Laura A. Velázquez-Villegas, Aurora Candelario-Martinez, Perla H. Horta-López, Armando Montoya-García, Gustavo Alberto Jaimes-Ortega, Luis Lopez-Bailon, Zayda Piedra-Quintero, Gabriela Carrasco-Torres, Marlon De Ita, Maria del Pilar Figueroa-Corona, José Esteban Muñoz-Medina, Magdalena Sánchez-Uribe, Marco Antonio Meraz-Ríos, Saúl Villa-Treviño, Francisco Garcia-Sierra, Bulmaro Cisneros, Michael Schnoor, Vianney F. Ortíz-Navarrete, Nicolás Villegas-Sepúlveda, Ricardo Valle-Rios, Oscar Medina-Contreras, Lilia G. Noriega, Porfirio Nava |
| Rok vydání: |
2023 |
| DOI: |
10.1101/2023.05.13.540666 |
| Popis: |
The quality of life in patients with inflammatory bowel diseases (IBD) is strongly impaired. Alterations of intestinal epithelial homeostasis contribute to the development and establishment of IBD. Intestinal Paneth and Paneth-like cells produce and secrete luminal proteins sustaining epithelial homeostasis. Here we show that IFN-γ stimulates Paneth and Paneth-like cells degranulation that triggers the proliferation of intestinal epithelial cells (IEC) in a Wnt/β-catenin independent manner. Degranulation in Paneth and Paneth-like cells was mTORC1 and necroptosis dependent. Remarkably, lack of IFN-γ, inhibition of mTORC1, or impeding necroptosis reduces IEC proliferation cytokine-mediated. Our findings identify a new role for IFN-γ in stimulating IEC proliferation through inducing degranulation of Paneth and Paneth-like cells which is mTORC1 and necroptosis- dependent. In a mouse model of colitis, mTORC1 activation and necroptosis regulate Paneth and Paneth-like cell secretion. Furthermore, the colitogenic environment triggers PC metaplasia in the distal region of the large intestine to simulate cell proliferation.Highlights:IFN-γ stimulates proliferation,β-catenin independent.IFN-γ enhances mitochondrial activity and proliferationIFN-γ regulates PC biogenesis.mTORC1-dependent necroptosis mediates secretion in Paneth and Paneth-like cells. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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