Shimada Shuichi, Makino Katsunari, Jinnin Masatoshi, Sawamura Soichiro, Kawano Yuya, Ide Maho, Kajihara Ikko, Makino Takamitsu, Fukushima Satoshi, Ihn Hironobu
Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
J Dermatol Sci. 2020 Dec;100(3):183-191. doi: 10.1016/j.jdermsci.2020.09.010. Epub 2020 Sep 29.
Systemic sclerosis (SSc) is characterized by excessive deposition of collagen in the skin and internal organs. Recent studies have shown that chemokine (C-X-C motif) ligands (CXCLs) are involved in the pathogenesis of SSc.
Our aim was to examine the anti-fibrotic potential of CXCL17, a newly discovered chemokine, in cultured skin fibroblasts and in a bleomycin-induced SSc mouse model. Moreover, we examined serum level of CXCL17 in patients with SSc.
Type I collagen expression was evaluated in SSc skin and cultured fibroblasts treated with CXCL17 using immunoblotting and quantitative reverse transcription-PCR. Serum CXCL17 levels were determined using enzyme-linked immunosorbent assay in 63 patients with SSc and 17 healthy subjects. A bleomycin-induced SSc mouse model was used to evaluate the effect of CXCL17 on skin fibrosis.
CXCL17 reduced the expression of type I collagen in healthy control fibroblasts. CXCL17 also induced matrix metalloproteinase 1 (MMP1) and miR-29 expression in fibroblasts, indicating that CXCL17 regulates type I collagen expression in part via post-transcriptional mechanisms through MMP1 and miR-29. We found that local injection of CXCL17 attenuated bleomycin-induced skin fibrosis in mice. CXCL17 levels in SSc skin were lower than those in healthy controls, in contrast to the high serum CXCL17 levels in patients with SSc. The low expression of CXCL17 in SSc skin possibly affects type I collagen accumulation in this disease.
Our data indicate that understanding CXCL17 signaling may lead to a better therapeutic approach for SSc.
系统性硬化症（SSc）的特征是皮肤和内脏器官中胶原蛋白过度沉积。最近的研究表明，趋化因子（C-X-C基序）配体（CXCLs）参与了SSc的发病机制。
我们的目的是在培养的皮肤成纤维细胞和博来霉素诱导的SSc小鼠模型中研究新发现的趋化因子CXCL17的抗纤维化潜力。此外，我们检测了SSc患者血清中CXCL17的水平。
使用免疫印迹法和定量逆转录PCR评估SSc皮肤和用CXCL17处理的培养成纤维细胞中I型胶原蛋白的表达。采用酶联免疫吸附测定法测定63例SSc患者和17名健康对照者血清CXCL17水平。使用博来霉素诱导的SSc小鼠模型评估CXCL17对皮肤纤维化的影响。
CXCL17降低了健康对照成纤维细胞中I型胶原蛋白的表达。CXCL17还诱导成纤维细胞中基质金属蛋白酶1（MMP1）和miR-29的表达，表明CXCL17部分通过MMP1和miR-29的转录后机制调节I型胶原蛋白的表达。我们发现局部注射CXCL17可减轻博来霉素诱导的小鼠皮肤纤维化。与健康对照相比，SSc皮肤中CXCL17水平较低，而SSc患者血清CXCL17水平较高。SSc皮肤中CXCL17的低表达可能影响该疾病中I型胶原蛋白的积累。
我们的数据表明，了解CXCL17信号通路可能会为SSc带来更好的治疗方法。
