Here's a recent abstract looking at over-expression of CTGF in IPF:
Eur Respir J 2001 Jun;17(6):1220-7 Related Articles, Books
Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF.
Pan LH, Yamauchi K, Uzuki M, Nakanishi T, Takigawa M, Inoue H, Sawai T.
First Dept of Pathology, Iwate Medical University School of Medicine, Morioka, Japan.
Connective tissue growth factor (CTGF) is a growth and chemotactic factor for fibroblasts encoded by an immediate early gene that is transcriptionally activated by transforming growth factor-beta. Previous studies have shown that both CTGF messenger ribonuclear acid (mRNA) and protein are expressed in renal fibrosis and bleomycin-induced pulmonary fibrosis in mice. The aim of the present study was to investigate the localization of CTGF protein and its mRNA expression in the fibrotic lung tissue of patients with idiopathic pulmonary fibrosis (IPF). Using human fibrotic lung tissue obtained from eight autopsy cases and four biopsy cases with IPF, immunohistochemical staining, in situ hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) were performed. The cellular immunoreactivity for CTGF was markedly increased in the lung tissue of patients with IPF, compared to normal lungs. The immunolocalization of CTGF was confined predominantly to proliferating type II alveolar epithelial cells and activated fibroblasts. In the normal lung, type II alveolar epithelial cells stained for CTGF were sparsely distributed. CTGF mRNA was localized in proliferating type II alveolar epithelial cells and activated fibroblasts in the interstitium of fibrotic lung tissues. RT-PCR analysis showed that CTGF mRNA was expressed at a higher level in fibrotic lungs than in normal lungs. In both an autocrine and a paracrine manner, type II alveolar epithelial cells and activated fibroblasts may play a critical role in pulmonary fibrosis by producing connective tissue growth factor which modulates fibroblast proliferation and extracellular matrix production.
Here we see IFN-gamma blocking one effect of a fibrosis-inducing chemical that normally up-regulates CTGF:
Arch Dermatol Res 2000 Nov;292(11):556-61 Related Articles, Books, LinkOut
Bleomycin increases steady-state levels of type I collagen, fibronectin and decorin mRNAs in human skin fibroblasts.
Yamamoto T, Eckes B, Krieg T.
Department of Dermatology, Tokyo Medical and Dental University, School of Medicine, Japan. yamamoto.derm@med.tmd.ac.jp
Bleomycin is a drug capable of inducing tissue fibrosis. In this study, the effects of bleomycin on gene expression of extracellular matrix encoding alpha1(I) collagen, fibronectin and decorin were determined in vitro in human dermal fibroblasts. Northern blot analysis showed that bleomycin upregulated alpha(I) collagen, fibronectin and decorin gene expression dose-dependently between 1 nM and 1 microM. Bleomycin at 100 nM upregulated alpha1(I) collagen, fibronectin and decorin mRNA expression with a peak at 6 h following stimulation in normal skin fibroblast monolayers. Bleomycin enhanced mRNA expression encoding these extracellular matrix proteins in both normal dermal and scleroderma fibroblasts. Concomitant stimulation with bleomycin and interferon-gamma (1,000 U/ml), a representative antifibrotic cytokine, decreased alpha1(I) collagen mRNA expression. Bleomycin also mildly upregulated mRNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) coordinately in normal skin fibroblasts. Our results indicate that bleomycin modulates gene expression of extracellular matrix proteins in dermal fibroblasts, and this effect may be mediated by TGF-beta and CTGF.
CTGF is also over-expressed in keloids - Connectics had a trial for keloids using IFN-gamma, but I don't know what became of it (or even who has the rights in dermatalogic applications).
Peter |
