Startseite
English
Erweiterte Suche
Durchblättern nach ...
Publikationen im Überblick
Ansprechpartner
Hilfe
DOI
PMC
 |
|
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
C/EBP homologous protein inhibits tissue repair in response to gut injury and is inversely regulated with chronic inflammation.
Mucosal Immunol. 7, 1452-1466 (2014)
Loss of intestinal epithelial cell (IEC) homeostasis and apoptosis negatively affect intestinal barrier function. Uncontrolled activation of the unfolded protein response (UPR) in IEC contributes to an impaired barrier and is implicated in the pathogenesis of inflammatory bowel diseases. However, the contribution of the UPR target gene C/EBP homologous protein (CHOP), an apoptosis-associated transcription factor, to inflammation-related disease susceptibility remains unclear. Consistent with observations in patients with ulcerative colitis, we show that despite UPR activation in the epithelium, CHOP expression was reduced in mouse models of T-cell-mediated and bacteria-driven colitis. To elucidate the molecular mechanisms of IEC-specific CHOP expression, we generated a conditional transgenic mouse model (Chop(IEC Tg/Tg)). Chop overexpression increased the susceptibility toward dextran sodium sulfate (DSS)-induced intestinal inflammation and mucosal tissue injury. Furthermore, a delayed recovery from DSS-induced colitis and impaired closure of mechanically induced mucosal wounds was observed. Interestingly, these findings seemed to be independent of CHOP-mediated apoptosis. In vitro and in vivo cell cycle analyses rather indicated a role for CHOP in epithelial cell proliferation. In conclusion, these data show that IEC-specific overexpression impairs epithelial cell proliferation and mucosal tissue regeneration, suggesting an important role for CHOP beyond mediating apoptosis.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Endoplasmic-reticulum Stress; Intestinal Epithelial-cells; Bowel-disease; Er Stress; Ulcerative-colitis; Chop Gadd153; Transcription Factors; Crohns-disease; Apoptosis; Mice
ISSN (print) / ISBN
1933-0219
e-ISSN
1933-0219
Zeitschrift
Mucosal Immunology
Quellenangaben
Band: 7,
Heft: 6,
Seiten: 1452-1466
Verlag
Nature Publishing Group
Verlagsort
UNITED STATES
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Virology (VIRO)