| Association of matrix metalloproteinase-3 with cardiogenic activity during Noggin-induced differentiation of mouse embryonic stem cells. | |
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MedLine Citation:
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PMID: 19138802 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Despite the pluripotency of embryonic stem (ES) cells, their clinical applications have been hindered due to the lack of reliable differentiation methods. Recently, it was shown that Noggin could effectively induce cardiomyocyte differentiation by transient treatment of ES cells. METHODS: To determine how Noggin may induce cardiac differentiation, we compared differentially expressed genes during Noggin-induced differentiation of ES cells using microarray analysis. We found Matrix metalloproteinase-3 (Mmp-3) expression was highly up-regulated by Noggin treatment. To understand the role of Mmp-3 in the cardiac differentiation of ES cells, we inhibited Mmp-3 activity by treating with a specific Mmp-3 inhibitor during Noggin-induced cardiac differentiation of ES cells. We also analyzed the expression levels of cardiac markers and the ratio of spontaneously beating embryoid bodies (EBs) in the presence of the Mmp-3 inhibitor. RESULTS: We analyzed EB samples from zero, two, and four days with or without Noggin treatment, and found that the expression levels of 2 (0 day), 56 (2 days), and 805 (4 days) genes were altered with Noggin treatment. Up-regulation of Mmp-3 was closely associated with relative increases of cardiogenic, vasculogenic, and hematopoietic genes in EB treated with Noggin. By inhibiting Mmp-3 activity, we verified that Mmp-3 activation is partly responsible for both the expression of cardiac markers and the elevated ratio of spontaneously beating to non-beating EBs. CONCLUSIONS: The concurrent expression of Mmp-3 with many cardiogenic genes and the specific inhibition of Mmp-3 revealed a critical role for Mmp-3 in Noggin-induced cardiac differentiation of ES cells. |
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Authors:
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Su Hong; Jae Ku Kang; Jung Jun Park; Eun Sook Ryu; Sung Sik Choi; Sang Ho Lee; Jong Ho Lee; Jeong-Sun Seo |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-12 |
Journal Detail:
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Title: International journal of cardiology Volume: 141 ISSN: 1874-1754 ISO Abbreviation: Int. J. Cardiol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-10 Completed Date: 2011-01-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8200291 Medline TA: Int J Cardiol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 49-60 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Macrogen Inc, World Meridian Venture Center, 60-24 Gasan-dong, Seoul 153-023, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carrier Proteins / physiology* Cell Differentiation / drug effects, physiology* Cells, Cultured Embryonic Stem Cells / cytology*, drug effects, enzymology* Hydroxamic Acids / pharmacology Matrix Metalloproteinase 3 / antagonists & inhibitors, biosynthesis*, genetics Mice Myocytes, Cardiac / cytology, drug effects, enzymology Oligopeptides / pharmacology Up-Regulation / drug effects, physiology |
| Chemical | |
Reg. No./Substance:
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0/4-aminobenzoyl-glycyl-prolyl-leucyl-alanine hydroxamic acid; 0/Carrier Proteins; 0/Hydroxamic Acids; 0/Oligopeptides; 148294-77-3/noggin protein; EC 3.4.24.17/Matrix Metalloproteinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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