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Beta-catenin overexpression reduces myocardial infarct size through differential effects on cardiomyocytes and cardiac fibroblasts

Cited 85 time in Web of Science Cited 88 time in Scopus
Authors
Hahn, Joo-Yong; Cho, Hyun-Ju; Bae, Jang-Whan; Yuk, Hyung-Sun; Kim, Kwang-Il; Park, Kyung-Woo; Koo, Bon-Kown; Chae, In-Ho; Shin, Chan-Soo; Oh, Byung-Hee; Choi, Yun-Shik; Park, Young-Bae; Kim, Hyo-Soo
Issue Date
2006-08-22
Publisher
American Society for Biochemistry and Molecular Biology
Citation
J Biol Chem. 2006 Oct 13;281(41):30979-89. Epub 2006 Aug 18.
Keywords
AnimalsCell CycleCyclin D1/metabolismFibroblasts/*metabolism*Gene Expression RegulationMyocardial Infarction/pathologyMyocardium/*metabolismMyocytes, Cardiac/*metabolismPhosphorylationProto-Oncogene Proteins c-bcl-2/metabolismRatsRats, Inbred F344Vascular Endothelial Growth Factor A/metabolismbeta Catenin/*biosynthesis
Abstract
Beta-catenin is a transcriptional regulator of several genes involved in survival and proliferation. Although previous studies suggest that beta-catenin may be involved in the process of preconditioning and healing after myocardial infarction (MI), little is known regarding the role of beta-catenin in cardiomyocytes and cardiac fibroblasts. We investigated the role of beta-catenin in cardiomyocytes and cardiac fibroblasts and whether beta-catenin overexpression could reduce MI size. Adenovirus-mediated gene transfer of nonphosphorylatable constitutively active beta-catenin (Ad-catenin) decreased apoptosis in cardiomyocytes and cardiac fibroblasts with increased expression of survivin and Bcl-2. Although Ad-catenin increased the percentage of cells in the S phase with enhanced expression of cyclin D1 and E2 in both cell types, the increase in cell number was only evident in cardiac fibroblasts, whereas hypertrophy and binuclear cells were more prominent in cardiomyocytes. All of these effects of beta-catenin gene transfer were blocked by inhibition of its nuclear translocation. Furthermore, Ad-catenin enhanced the expression of vascular endothelial growth factor in both cells and induced differentiation of cardiac fibroblasts into myofibroblasts. In a rat MI model, injection of Ad-catenin into the infarct border zone resulted in a significantly decreased MI size with anti-apoptotic effect and cell cycle activation in both cardiomyocytes and myofibroblasts. beta-Catenin may play an important role in the healing process after MI by promoting survival and cell cycle not only in cardiomyocytes but also in cardiac fibroblasts with its differentiation into myofibroblasts.
ISSN
0021-9258 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16920707

http://hdl.handle.net/10371/29654
DOI
https://doi.org/10.1074/jbc.M603916200
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Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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