Role and interaction of connective tissue growth factor with transforming growth factor-β in persistent fibrosis: A mouse fibrosis model

Toshifumi Mori, Shigeru Kawara, Mikio Shinozaki, Nobukazu Hayashi, Takashi Kakinuma, Atsuyuki Igarashi, Masaharu Takigawa, Toru Nakanishi, Kazuhiko Takehara

Research output: Contribution to journalArticle

388 Citations (Scopus)

Abstract

Skin fibrotic disorders are understood to develop under the influence of some growth factors, such as transforming growth factor-beta (TGF-β), basic fibroblast growth factor (bFGF), or connective tissue growth factor (CTGF). To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, we investigated the in vivo effects of growth factors by injecting TGF-β, CTGF, and bFGF into the subcutaneous tissue of newborn mice. A single application of TGF-β or bFGF resulted in the formation of transient granulated tissue that disappeared despite 7 days of consecutive injections. A single CTGF injection also caused slight granulation. However, injecting TGF-β plus CTGF produced long-term fibrotic tissue, which persisted for at least 14 days. Also, fibrotic tissue was observed when CTGF was injected from 4 to 7 days after TGF-β injections for the first 1-3 days. In situ hybridization analysis revealed the expression of CTGF mRNA in the fibroblasts at least in a few fibrotic conditions. These findings suggest that either CTGF mRNA or an application of exogenous CTGF protein is required for the development of persistent fibrosis. From our study, it appears that interaction of several growth factors is required for persistent fibrotic tissue formation, with TGF-β causing the induction and CTGF needed for maintenance of skin fibrosis. The animal model on skin fibrosis by exogenous application of growth factors developed in this study may prove useful for future studies on fibrotic disorders.

Original languageEnglish
Pages (from-to)153-159
Number of pages7
JournalJournal of cellular physiology
Volume181
Issue number1
DOIs
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Role and interaction of connective tissue growth factor with transforming growth factor-β in persistent fibrosis: A mouse fibrosis model'. Together they form a unique fingerprint.

  • Cite this