Stem Cells http://www.peprotech.com/
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

First published online September 4, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Google Scholar
Right arrow Articles by Suga, H.
Right arrow Articles by Yoshimura, K.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Suga, H.
Right arrow Articles by Yoshimura, K.
Submitted on March 20, 2008
Accepted on August 28, 2008

TISSUE-SPECIFIC STEM CELLS

IFATS Series: FGF-2-induced HGF Secretion By Adipose-Derived Stromal Cells Inhibits Post-Injury Fibrogenesis Through A JNK-Dependent Mechanism

Hirotaka Suga 1, Hitomi Eto 1, Tomokuni Shigeura 2, Keita Inoue 1, Noriyuki Aoi 1, Harunosuke Kato 1, Satoshi Nishimura 3, Ichiro Manabe 4, Koichi Gonda 1, Kotaro Yoshimura 1*

1 Department of Plastic Surgery, University of Tokyo, Tokyo, Japan
2 Division of Research and Development, Biomaster Inc., Kanagawa, Japan
3 Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan
4 Nano-Bioengineering Education Program, University of Tokyo, Tokyo, Japan; PRESTO, Japan Science and Technology Agency, Tokyo, Japan

* To whom correspondence should be addressed. E-mail: yoshimura-pla{at}h.u-tokyo.ac.jp.


  Abstract

Background: Adipose-derived stem/stromal cells (ASCs) not only function as tissue-specific progenitor cells, but are also multipotent and secrete angiogenic growth factors such as hepatocyte growth factor (HGF) under certain circumstances. However, the biological role and regulatory mechanism of this secretion have not been well studied.

Methods and Results: We focused on the role of ASCs in the process of adipose tissue injury and repair, and found that among injury-associated growth factors, fibroblast growth factor-2 (FGF-2) strongly promoted ASC proliferation and HGF secretion through a c-Jun N-terminal kinase (JNK) signaling pathway. In a mouse model of ischemiareperfusion injury of adipose tissue, regenerative changes following necrotic and apoptotic changes were seen for 2 weeks. Acute release of FGF-2 by injured adipose tissue was followed by upregulation of HGF. During the adipose tissue remodeling process, adipose-derived BrdU-positive cells were shown to be ASCs (CD31–CD34+). Inhibition of JNK signaling inhibited the activation of ASCs and delayed the remodeling process. In addition, inhibition of FGF-2 or JNK signaling prevented post-injury upregulation of HGF and led to increased fibrogenesis in the injured adipose tissue. Increased fibrogenesis also followed the administration of a neutralizing antibody against HGF.

Conclusions: FGF-2 released from injured tissue acts through a JNK signaling pathway to stimulate ASCs to proliferate and secrete HGF, contributing to the regeneration of adipose tissue and suppression of fibrogenesis after injury. This study revealed a functional role for ASCs in the response to injury and provides new insight into the therapeutic potential of ASCs.

______________________________________________________________________________

Author contributions: H.S.: Collection and/or assembly of data, Data analysis and interpretation, Manuscript writing; H.E.: Collection and/or assembly of data; T.S.: Collection and/or assembly of data; K.I.: Collection and/or assembly of data; N.A.: Collection and/or assembly of data; H.K.: Collection and/or assembly of data; S.N.: Data analysis and interpretation; I.M.: Data analysis and interpretation; K.G.: Data analysis and interpretation; K.Y.: Conception and design, Financial support, Administrative support, Collection and/or assembly of data, Data analysis and interpretation, Manuscript writing.

 Key Words. Adipose-derived stem cells, Hepatocyte growth factor, Fibroblast growth factor-2, c-Jun N-terminal kinase, Fibrogenesis, Ischemia-reperfusion injury






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
STEM CELLS THE ONCOLOGIST CME ALPHAMED PRESS JOURNALS

Copyright © 2008 by AlphaMed Press.