Id1 expression in endothelial cells of the colon is required for normal response to injury Journal Article

Authors: Zhang, N.; Subbaramaiah, K.; Yantiss, R. K.; Zhou, X. K.; Chin, Y.; Scherl, E. J.; Bosworth, B. P.; Benezra, R.; Dannenberg, A. J.
Article Title: Id1 expression in endothelial cells of the colon is required for normal response to injury
Abstract: Inhibitor of DNA binding (ID)-1 is important for angiogenesis during embryogenesis and tumor development. Whether ID1 expression in endothelial cells of the colon is required for normal response to injury is unknown. We demonstrate that Id1 is up-regulated in colonic endothelial cells in an experimental model of colitis and in the inflamed mucosa of patients with inflammatory bowel disease. Because prostaglandin E2 and tumor necrosis factor-α are also elevated in colitis, we determined whether these factors could induce ID1 transcription in cultured endothelial cells. Tumor necrosis factor-α stimulated ID1 transcription via early growth response 1 protein (Egr-1). By contrast, the induction of ID1 by prostaglandin E2 was mediated by cAMP response element-binding protein (CREB). To determine whether the increased ID1 levels in the endothelial cells of inflamed mucosa were an adaptive response that modulated the severity of tissue injury, Id1 was conditionally depleted in the endothelium of mice, which sensitized the mice to more severe chemical colitis, including more severe diarrhea, bleeding, and histological injury, and shorter colon compared with control mice. Moreover, depletion of Id1 in the vasculature was associated with increased CD31+ aggregates and increased vascular permeability in inflamed mucosa compared with those in Id1 wild-type control mice. These results suggest that endothelial ID1 up-regulation in inflamed colonic mucosa is an adaptive response that modulates the severity of tissue injury. © 2015 American Society for Investigative Pathology.
Keywords: controlled study; protein expression; human cell; histopathology; diarrhea; nonhuman; comparative study; mouse; animal tissue; disease association; inhibitor of differentiation 1; protein depletion; mucosa inflammation; animal experiment; animal model; vascularization; wild type; disease severity; tumor necrosis factor alpha; cell culture; prostaglandin e2; clinical evaluation; intestine epithelium cell; upregulation; tissue injury; transient transfection; membrane permeability; cd31 antigen; cyclic amp responsive element binding protein; colon mucosa; intestinal bleeding; early growth response factor 1; blood vessel permeability; human; male; priority journal; article; experimental colitis; protein aggregate; colonic endothelial cell; shorter colon
Journal Title: American Journal of Pathology
Volume: 185
Issue: 11
ISSN: 0002-9440
Publisher: Elsevier Science, Inc.  
Date Published: 2015-11-01
Start Page: 2983
End Page: 2993
Language: English
DOI: 10.1016/j.ajpath.2015.07.005
PROVIDER: scopus
PMCID: PMC4630175
PUBMED: 26348574
Notes: Export Date: 2 December 2015 -- Source: Scopus
Citation Impact
MSK Authors
  1. Robert Benezra
    144 Benezra
  2. Yvette Chin
    12 Chin
  3. Ning Zhang
    3 Zhang