CTRP6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts
Introduction
Burn injuries are one of the most common reasons for illness and death in the world. The prevalence of burns in the general population is high [1]. Skin burn carries a large burden of disease, including disfigurement, pain and disability [2]. Currently there are no clinically effective treatments for skin burn. Fibroblast-to-myofibroblast transition is a key event during wound healing and scar formation. Fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of extracellular matrix (ECM) in skin [3]. Transforming growth factor-β (TGF-β) is the most potent inducer of fibroblast activation and ECM synthesis in skin fibrosis [4]. Therefore, blockade of TGF-β1/Smad signaling pathway suppresses collagen production and eventually alleviates skin fibrosis.
C1q/tumor necrosis factor-related proteins (CTRPs), a new highly conserved family of adiponectin paralogs, are involved in diverse processes including metabolism, inflammation host defense, apoptosis, cell differentiation, autoimmunity, hibernation and organogenesis [5], [6], [7], [8]. CTRP6, a member of CTRPs, is a glycoprotein of molecular mass of 29 kDa consisting of four domains (signal peptide, short N-terminal variable region, collagen domain and C-terminal C1q domain) [9]. Growing body of evidence suggests that CTRP6 plays an important role in adipogenesis, inflammatory reaction, fatty acid metabolism and carcinogenesis [10], [11], [12]. For example, Kim et al. reported that CTRP6 induces the expression of interleukin-10 (IL-10) in macrophages [13]. Recently, one study showed that CTRP6 improved cardiac function, attenuated cardiac hypertrophy, alleviated cardiac fibrosis, and inhibited myofibroblast differentiation as well as the expression of collagen I, collagen III, and connective tissue growth factor post-myocardial infarction. However, the function and detailed regulatory mechanism of CTRP6 in skin fibrosis remain unclear. The aim of this study was to investigate the effect of CTRP6 on the activation of human dermal fibroblasts.
Section snippets
Tissue specimens
Skin tissues were collected from seven burn patients who had undergone surgical excision in Shaanxi Provincial People’s Hospital (China). Normal skin tissues were obtained from seven healthy volunteers. Prior written informed consent was obtained from the patients and the study was conducted according to the principles of the Declaration of Helsinki and was approved by the Research Ethical Committee of Shaanxi Provincial People’s Hospital.
Cell culture and treatment
Primary culture of dermal fibroblasts was established as
CTRP6 expression was decreased in scar tissues and TGF-β1-treated dermal fibroblasts
We first detected the expression of CTRP6 in scar tissues by qRT-PCR. The results demonstrated that the expression levels of CTRP6 mRNA were lower in scar tissues from burn patients than in normal tissues from control patients (Fig. 1A). Also, we, we examined the expression of CTRP6 in dermal fibroblasts after TGF-β1 treatment. As shown Fig. 1B, CTRP6 mRNA expression was decreased by TGF-β1. Similarly, Western blot analysis demonstrated that TGF-β1 treatment greatly decreased CTRP6 protein
Discussion
Skin fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of ECM. In this study, we found that CTRP6 was lowly expressed in scar tissues and TGF-β1-treated dermal fibroblasts. CTRP6 overexpression significantly inhibited the proliferation of dermal fibroblasts, as well as suppressed the expression of ECM in TGF-β1-treated dermal fibroblasts. Furthermore, CTRP6 overexpression markedly inhibited TGF-β1-induced phosphorylation of Smad3 in dermal fibroblasts.
CTRP6
Conflicts of interest
The authors declare that they have no conflict of interest.
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