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Cathepsin L derived from skeletal muscle cells transfected with bFGF promotes endothelial cell migration

Authors
 Ji Hyung Chun  ;  Eun Kyoung Im  ;  Yangsoo Jang  ;  Kyung Hye Lee  ;  Min-Jeong Shin  ;  Eun Young Choi  ;  Soo Hyuk Kim  ;  Seung-Min Lee  ;  Taewon Jin 
Citation
 Experimental and Molecular Medicine, Vol.43(4) : 179-188, 2011 
Journal Title
 Experimental and Molecular Medicine 
ISSN
 1226-3613 
Issue Date
2011
Abstract
Gene transfer of basic fibroblast growth factor (bFGF) has been shown to induce significant endothelial migration and angiogenesis in ischemic disease models. Here, we investigate what factors are secreted from skeletal muscle cells (SkMCs) transfected with bFGF gene and whether they participate in endothelial cell migration. We constructed replication-defective adenovirus vectors containing the human bFGF gene (Ad/bFGF) or a control LacZ gene (Ad/LacZ) and obtained conditioned media, bFGF-CM and LacZ-CM, from SkMCs infected by Ad/bFGF or Ad/LacZ, respectively. Cell migration significantly increased in HUVECs incubated with bFGF-CM compared to cells incubated with LacZ-CM. Interestingly, HUVEC migration in response to bFGF-CM was only partially blocked by the addition of bFGF-neutralizing antibody, suggesting that bFGF-CM contains other factors that stimulate endothelial cell migration. Several proteins, matrix metalloproteinase-1 (MMP-1), plasminogen activator inhibitor-1 (PAI-1), and cathepsin L, increased in bFGF-CM compared to LacZ-CM; based on 1-dimensional gel electrophoresis and mass spectrometry. Their increased mRNA and protein levels were confirmed by RT-PCR and immunoblot analysis. The recombinant human bFGF protein induced MMP-1, PAI-1, and cathepsin L expression in SkMCs. Endothelial cell migration was reduced in groups treated with bFGF-CM containing neutralizing antibodies against MMP-1 or PAI-1. In particular, HUVECs treated with bFGF-CM containing cell-impermeable cathepsin L inhibitor showed the most significant decrease in cell migration. Cathepsin L protein directly promotes endothelial cell migration through the JNK pathway. These results indicate that cathepsin L released from SkMCs transfected with the bFGF gene can promote endothelial cell migration.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/93285
DOI
10.3858/emm.2011.43.4.022
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Cardiovascular Product Evaluation Center (심혈관제품유효성평가센터)
Yonsei Authors
김수혁(Kim, Soo Hyuk) ; 이경혜(Lee, Kyung Hye) ; 임은경(Im, Eun Kyoung) ; 장양수(Jang, Yang Soo) ; 정지형(Chung, Ji Hyung) ; 진태원(Jin, Tae Won) ; 최은영(Choi, Eun Young)
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