| Activation of the sonic hedgehog signaling controls human pulmonary arterial smooth muscle cell proliferation in response to hypoxia. | |
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MedLine Citation:
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PMID: 20840857 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The hedgehog signal pathway plays a crucial role in the angiogenesis and vascular remodeling. However, the function of this pathway in the pulmonary vascular smooth cell proliferation in response to hypoxia remains unknown. In this study, we have demonstrated that the main components of the hedgehog pathway, including sonic hedgehog (SHH), patched1 (PTCH1), smoothened (SMO), GLI and hypoxia-inducible factor 1 (HIF1) are expressed in the human pulmonary arterial smooth muscle cells (HPASMCs). Interestingly, hypoxia significantly enhanced the expression of SHH and HIF1, facilitated the translocation of GLI1 into the nuclei, and promoted the proliferation of HPASMCs. Furthermore, direct activation of the SHH pathway through incubation with the purified recombinant human SHH or with purmorphamine and SAG, two Smo agonists, also enhanced the proliferation of HPASMCs. Importantly, the treatment with anti-SHH and anti-HIF1 antibodies or cyclopamine, a specific SMO inhibitor, markedly inhibited the nuclear translocation of GLI1 and cell proliferation in the HPASMCs induced by hypoxia and activation of the SHH pathway. Moreover, the treatment with cyclopamine increased apoptosis in the hypoxic HPASMCs. These data strongly demonstrate for the first time that the SHH signaling plays a crucial role in the regulation of HPASMC growth in response to hypoxia. |
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Authors:
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Guansong Wang; Zhiyuan Zhang; Zhi Xu; Hongjin Yin; Li Bai; Zhuang Ma; Mark A Decoster; Guisheng Qian; Guangyu Wu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-15 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1803 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-10-18 Completed Date: 2010-12-10 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1359-67 Citation Subset: IM |
Affiliation:
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Institute of Respiratory Diseases, Xinqiao Hospital of the Third Military Medical University, Chongqing 400037, P.R. China; Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anoxia
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pathology* Hedgehog Proteins / metabolism* Humans Lung / cytology* Muscle, Smooth, Vascular / cytology* Signal Transduction* |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM076167-05/GM/NIGMS NIH HHS; R01GM076167/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hedgehog Proteins; 0/SHH protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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