E-GEOD-36056 - Transcriptional profiling of intestinal samples from Atg4b knock-out mice during chemical-induced colitis
Released on 16 September 2013, last updated on 26 September 2013
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 autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase paralleling 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’s disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b-/- mice. Taken together, these results provide additional evidence on 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 Seven samples were collected in total: three from wild-type mice (1 from the ileum and the colon of control mice, and 1 from the colon of a DSS-treated mouse) and four from Atg4b knock-out mice (1 from the ileum and the colon of control mice, and 2 from the colon of DSS-treated mice).
transcription profiling by array
Alvaro F Fernandez <email@example.com>, Carlos Lopez-Otin, Guillermo Mariño, José M Freije, Sandra Cabrera, Álvaro F Fernández
ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis. Cabrera S, Fernï¿½ndez AF, Mariï¿½o G, Aguirre A, Suï¿½rez MF, Espaï¿½ol Y, Vega JA, Laurï¿½ R, Fueyo A, Fernï¿½ndez-Garcï¿½a MS, Freije JM, Kroemer G, Lï¿½pez-Otï¿½n C. , Europe PMC 23782979