ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis
| Autor: | Álvaro F. Fernández, Rosaria Laurà, María F. Suárez, José M.P. Freije, Guillermo Mariño, Antonio Fueyo, M. Soledad Fernández-García, Carlos López-Otín, Sandra Cabrera, Guido Kroemer, Alina Aguirre, José A. Vega, Yaiza Español |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Paneth Cells
Autophagy-Related Proteins Inflammation ATG4B Paneth cell autophagin-1 autophagy colitis cysteine peptidase inflammation intestinal homeostasis Biology Inflammatory bowel disease Proinflammatory cytokine Mice Ileum autophagin-1 medicine Autophagy Animals Homeostasis Colitis Intestinal Mucosa Molecular Biology Tissue homeostasis Paneth cell Dextran Sulfate intestinal homeostasis Cell Biology medicine.disease Inflammatory Bowel Diseases Ulcerative colitis Basic Research Paper Anti-Bacterial Agents Hematopoiesis ATG4B Intestines Mice Inbred C57BL Cysteine Endopeptidases medicine.anatomical_structure inflammation Immunology Cytokines Disease Susceptibility medicine.symptom Inflammation Mediators cysteine peptidase |
| Zdroj: | SCOPUS RUO. Repositorio Institucional de la Universidad de Oviedo instname |
| Popis: | The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b (-/-) mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b (-/-) mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency. |
| Databáze: | OpenAIRE |
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