Jing J, Dou T T, Yang J Q, Chen X B, Cao H L, Min M, Cai S Q, Zheng M, Man X Y
Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Eur Cytokine Netw. 2015 Jan-Mar;26(1):10-4. doi: 10.1684/ecn.2015.0360.
Endothelin-1 (ET-1) acts as a key regulator of vasoconstriction and fibrosis. Many previous studies have focused on the role of ET-1 in scleroderma (systemic sclerosis, SSc). We investigated the effects of ET-1 on the production of extracellular matrix in SSc and normal skin fibroblasts. Primary cultured dermal fibroblasts from SSc patients and healthy controls were treated with ET-1 (25 ng/mL) for 0 min, 15 min, 1 h, 24 h, 48 h and 72 h, respectively. Our results showed that, in SSc fibroblasts, ET-1 upregulated collagen type I, connective tissue growth factor (CTGF), type I plasminogen activator inhibitor (PAI-1) and pAkt in a time-dependent manner within 72 h; in normal fibroblasts, 25 ng/mL ET-1 stimulation correlated with high levels of CTGF, PAI-1 and pAkt. The secretion of fibronectin (FN), collagen type I, and PAI-1 is markedly increased in the supernatant of both SSc fibroblasts and normal fibroblasts. Furthermore, ET-1 phosphorylates Smad2 and Smad3 in normal fibroblasts, but not in SSc fibroblasts. In conclusion, our results demonstrated that ET-1 may induce fibrosis in dermal fibroblasts through Akt signals.
内皮素 -1（ET -1）是血管收缩和纤维化的关键调节因子。此前许多研究聚焦于ET -1在硬皮病（系统性硬化症，SSc）中的作用。我们研究了ET -1对SSc和正常皮肤成纤维细胞中细胞外基质产生的影响。分别用ET -1（25 ng/mL）处理来自SSc患者和健康对照者的原代培养真皮成纤维细胞0分钟、15分钟、1小时、24小时、48小时和72小时。我们的结果表明，在SSc成纤维细胞中，ET -1在72小时内以时间依赖性方式上调I型胶原蛋白、结缔组织生长因子（CTGF）、I型纤溶酶原激活物抑制剂（PAI -1）和磷酸化Akt；在正常成纤维细胞中，25 ng/mL ET -1刺激与高水平的CTGF、PAI -1和磷酸化Akt相关。在SSc成纤维细胞和正常成纤维细胞的上清液中，纤连蛋白（FN）、I型胶原蛋白和PAI -1的分泌均显著增加。此外，ET -1使正常成纤维细胞中的Smad2和Smad3磷酸化，但不使SSc成纤维细胞中的Smad2和Smad3磷酸化。总之，我们的结果表明ET -1可能通过Akt信号诱导真皮成纤维细胞纤维化。
