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면역미생물공생연구단
면역 미생물 공생 연구단
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HIF-1 alpha activation in myeloid cells accelerates dextran sodium sulfate-induced colitis progression in mice

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Title
HIF-1 alpha activation in myeloid cells accelerates dextran sodium sulfate-induced colitis progression in mice
Author(s)
Young-Eun Kim; Minji Lee; Hyejung Gu; Jeongwoo Kim; Seongju Jeong; Sujin Yeo; You Jeong Lee; Sin-Hyeog Im; Young-Chul Sung; Hak Jae Kim; Irving L. Weissman; G-One Ahn
Publication Date
2018-07
Journal
Disease Models & Mechanisms, v.11, no.7, pp.1 - 12
Publisher
COMPANY BIOLOGISTS LTD
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease, in which the intestinal epithelium loses its barrier function. Given the existence of the oxygen gradient in the intestinal epithelium and that inflammation further contributes to the tissue hypoxia, we investigated the role of hypoxia-inducible factor (HIF), a transcription factor activated under hypoxic conditions in myeloid cells, in the progression of IBD. To do this, we utilized myeloid-specific knockout (KO) mice targeting HIF pathways, created by a Cre-loxP system with human MRP8 (hMRP8), an intracellular calcium-binding protein, as the myeloid promoter. By feeding 5% dextran sodium sulfate (DSS) to hMRP8 von Hippel Lindau (Vhl) KO mice, in which HIF-1 alpha and HIF-2 alpha are constitutively activated in myeloid cells, we found that these mice were highly susceptible to DSS-induced colitis, demonstrating greater body weight loss, increased mortality, faster onset of rectal bleeding, shortened colon length, and increased CD11b- or Gr-1-positive myeloid cells in the colon compared with wild-type (WT) mice. These parameters were restored to, if not better than, the WT levels when we examined hMRP8 Hif-1a KO mice upon 5% DSS feeding. hMRP8 Hif-2a KO mice, on the other hand, exhibited a similar degree of DSS-induced colitis to that of WT mice. Lastly, when DSS was given together with azoxymethane to induce tumorigenesis in the colon, we found that hMRP8 Hif-1a KO mice exhibited comparable levels of colorectal tumors to those of WT mice, indicating that HIF-1 alpha in myeloid cells is dispensable for tumorigenesis. Collectively, our results suggest that HIF-1 alpha activation in myeloid cells critically regulates IBD progression
URI
https://pr.ibs.re.kr/handle/8788114/4964
ISSN
1754-8403
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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