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题名: The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to hypoxia and extracellular matrix injury
作者: Vozdek, Roman1, 2; Long, Yong1, 2, 3; Ma, Dengke K.1, 2
刊名: SCIENCE SIGNALING
发表日期: 2018-10-02
DOI: 10.1126/scisignal.aat0138
卷: 11, 期:550
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
英文摘要: Inadequate tissue oxygen, or hypoxia, is a central concept in the pathophysiology of ischemic disorders and cancer. Hypoxia promotes extracellular matrix (ECM) remodeling, cellular metabolic adaptation, and cancer cell metastasis. To discover new pathways through which cells respond to hypoxia, we performed a large-scale forward genetic screen in Caenorhabditis elegans and identified a previously uncharacterized receptor tyrosine kinase named HIR-1. Loss of function in hir-1 phenocopied the impaired ECM integrity associated with hypoxia or deficiency in the oxygen-dependent dual oxidase, heme peroxidases, or cuticular collagens involved in ECM homeostasis. Genetic suppressor screens identified NHR-49 and MDT-15 as transcriptional regulators downstream of HIR-1. Furthermore, hir-1 mutants showed defects in adapting to and recovering from prolonged severe hypoxia. We propose that C. elegans HIR-1 coordinates hypoxia-inducible factor-independent responses to hypoxia and hypoxia-associated ECM remodeling through mechanisms that are likely conserved in other organisms.
关键词[WOS]: NEMATODE CAENORHABDITIS-ELEGANS ; C-ELEGANS ; OXYGEN DEPRIVATION ; STRESS-RESPONSE ; GENE ONTOLOGY ; GROWTH-FACTOR ; HYDROXYLASE ; CUTICLE ; CANCER ; PROLYL
语种: 英语
项目资助者: NIH(R01GM117461 ; American Diabetes Association grant(1-16-IBS-197) ; Pew Scholar Award ; Alfred P. Sloan Foundation Fellowship ; Packard Fellowship in Science and Engineering ; Larry L. Hillblom start-up grant ; Larry L. Hillblom fellowship ; R00HL116654)
WOS记录号: WOS:000446086600002
ISSN号: 1945-0877
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内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/56146
Appears in Collections:其他_期刊论文

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作者单位: 1.Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA
2.Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA
3.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei, Peoples R China
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