Abstract
BackgroundSystemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs. Although the involvement of connective tissue growth factor (CTGF/CCN2) has been well-documented in SSc fibrosis, the therapeutic potential of targeting CTGF in SSc has not been fully investigated. Our aim was to examine the therapeutic potential of CTGF blockade in a preclinical model of SSc using two approaches: smooth muscle cell fibroblast-specific deletion of CTGF (CTGF knockout (KO)) or a human anti-CTGF monoclonal antibody, FG-3019.MethodsAngiotensin II (Ang II) was administered for 14 days by subcutaneous osmotic pump to CTGF KO or C57BL/6 J mice. FG-3019 was administered intraperitoneally three times per week for 2 weeks. Skin fibrosis was evaluated by histology and hydroxyproline assay. Immunohistochemistry staining was used for alpha smooth muscle actin (αSMA), platelet-derived growth factor receptor β (PDGFRβ), pSmad2, CD45, von Willebrand factor (vWF), and immunofluorescence staining was utilized for procollagen and Fsp1.ResultsAng II-induced skin fibrosis was mitigated in both CTGF KO and FG-3019-treated mice. The blockade of CTGF reduced the number of cells expressing PDGFRβ, procollagen, αSMA, pSmad2, CD45, and Fsp1 in the dermis. In addition, inhibition of CTGF attenuated vascular injury as measured by the presence of vWF-positive cells.ConclusionsOur data indicate that inhibition of CTGF signaling presents an attractive therapeutic approach in SSc.
Highlights
Systemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs
Fibroblast-specific deletion of connective tissue growth factor (CTGF) alleviates Ang IIinduced skin fibrosis To evaluate the therapeutic effects of CTGF blockade in the in vivo model of SSc, we used a mouse model of Ang Angiotensin II (II)-induced skin fibrosis [17]
Angiotensin II (Ang II)-induced skin fibrosis is accompanied by diverse pathogenic mechanisms, including collagen accumulation, CTGF upregulation, myofibroblast accumulation, endothelial cell injury, inflammation, and fibrosis [15,16,17]
Summary
Systemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs. The involvement of connective tissue growth factor (CTGF/CCN2) has been well-documented in SSc fibrosis, the therapeutic potential of targeting CTGF in SSc has not been fully investigated. Systemic sclerosis (SSc) is a multisystem connective tissue disorder that typically results in fibrosis of the skin and internal organs [1]. Connective tissue growth factor (CTGF, known as CCN2), a member of the CCN family of matricellular proteins, is widely known as a hallmark of fibrosis in multiple tissues, including skin, heart, lung, liver, and kidney [3, 4]. Further support was provided by a recent study that showed that fibroblast-specific ablation of CTGF inhibited development of dermal fibrosis in the bleomycin injection model [6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
