%0 Journal Article
%T Cooperative interaction of CTGF and TGF-¦Â in animal models of fibrotic disease
%A Qingjian Wang
%A William Usinger
%A Blake Nichols
%A Julia Gray
%A Leon Xu
%A Todd W Seeley
%A Mitch Brenner
%A Guangjie Guo
%A Weihua Zhang
%A Noelynn Oliver
%A Al Lin
%A David Yeowell
%J Fibrogenesis & Tissue Repair
%D 2011
%I BioMed Central
%R 10.1186/1755-1536-4-4
%X Intraperitoneal coadministration of CTGF and TGF-¦Â2 elicited a profound fibrotic response that was inhibited by the human anti-CTGF antibody FG-3019, as indicated by the ability of FG-3019 to ameliorate the histologic signs of fibrosis and reduce the otherwise increased hydroxyproline:proline (Hyp:Pro) ratios by 25% in kidney (P < 0.05), 30% in liver (P < 0.01) and 63% in lung (P < 0.05). Moreover, administration of either cytokine alone failed to elicit a fibrotic response, thus demonstrating that CTGF is both necessary and sufficient to initiate fibrosis in the presence of TGF-¦Â and vice versa. In keeping with this requirement for CTGF function in fibrosis, FG-3019 also reduced the renal Hyp:Pro response up to 20% after UUO (P < 0.05). In bleomycin-injured animals, a similar trend towards a FG-3019 treatment effect was observed (38% reduction in total lung Hyp, P = 0.056). Thus, FG-3019 antibody treatment consistently reduced excessive collagen deposition and the pathologic severity of fibrosis in all models.Cooperative interactions between CTGF and TGF-¦Â signaling are required to elicit overt tissue fibrosis. This interdependence and the observed anti-fibrotic effects of FG-3019 indicate that anti-CTGF therapy may provide therapeutic benefit in different forms of fibroproliferative disease.Fibroproliferative diseases, including chronic pulmonary, hepatic, renal and vascular fibrosis, contribute to nearly half of all deaths in the USA[1,2]. These disorders frequently affect multiple organ systems, complicating the elucidation of their underlying pathogenesis and hindering the development of effective treatments. Nevertheless, two secreted factors, transforming growth factor (TGF-¦Â and connective tissue growth factor (CTGF), are widely regarded as universal mediators of fibrogenesis, although the precise mechanisms that underlie their concerted effects remain unclear [3-8]. Because TGF-¦Â is a potent inducer of CTGF, most models postulate that CTGF acts as a downstr
%U http://www.fibrogenesis.com/content/4/1/4