Yeyi Zheng , Wenjie Gong , Zhaohang Wu , Siyi Zhang , Nan Wang , Zhenyu Hu , Yanni Shou , Tianpeng Xu , Yingjie Shen , Xiaokun Li , Litai Jin , Weitao Cong , Zhongxin Zhu
{"title":"FGF21通过抑制CK2α/GLI2信号轴改善成纤维细胞活化和系统性硬化症","authors":"Yeyi Zheng , Wenjie Gong , Zhaohang Wu , Siyi Zhang , Nan Wang , Zhenyu Hu , Yanni Shou , Tianpeng Xu , Yingjie Shen , Xiaokun Li , Litai Jin , Weitao Cong , Zhongxin Zhu","doi":"10.1016/j.jid.2024.07.026","DOIUrl":null,"url":null,"abstract":"<div><div>Systemic sclerosis is a typical fibrotic disease of unknown etiology that is characterized by abnormal fibroblast activation and excessive deposition of extracellular matrix. Unfortunately, effective therapeutic approaches are lacking. FGF21 plays a key role in mediating a variety of biological activities. However, its specific function in systemic sclerosis is unclear. In this study, we found that the expression of FGF21 was significantly downregulated in fibrotic skin tissue and in TGF-β–stimulated fibroblasts. Furthermore, our studies demonstrated that treatment with recombinant FGF21 in the skin significantly alleviated bleomycin-induced and TBRI-activated fibrosis and inhibited the activation of fibroblasts, whereas skin fibrosis was exacerbated by deletion of FGF21. Mechanistically, FGF21 inhibits the activity of CK2α and promotes the degradation of GLI2. In conclusion, these results indicate that FGF21 attenuates skin fibrosis through the CK2α/GLI2 signaling pathway and therefore may be a potential therapeutic target for systemic sclerosis.</div></div>","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"145 4","pages":"Pages 842-853.e8"},"PeriodicalIF":5.7000,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"FGF21 Ameliorates Fibroblasts Activation and Systemic Sclerosis by Inhibiting CK2α/GLI2 Signaling Axis\",\"authors\":\"Yeyi Zheng , Wenjie Gong , Zhaohang Wu , Siyi Zhang , Nan Wang , Zhenyu Hu , Yanni Shou , Tianpeng Xu , Yingjie Shen , Xiaokun Li , Litai Jin , Weitao Cong , Zhongxin Zhu\",\"doi\":\"10.1016/j.jid.2024.07.026\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Systemic sclerosis is a typical fibrotic disease of unknown etiology that is characterized by abnormal fibroblast activation and excessive deposition of extracellular matrix. Unfortunately, effective therapeutic approaches are lacking. FGF21 plays a key role in mediating a variety of biological activities. However, its specific function in systemic sclerosis is unclear. In this study, we found that the expression of FGF21 was significantly downregulated in fibrotic skin tissue and in TGF-β–stimulated fibroblasts. Furthermore, our studies demonstrated that treatment with recombinant FGF21 in the skin significantly alleviated bleomycin-induced and TBRI-activated fibrosis and inhibited the activation of fibroblasts, whereas skin fibrosis was exacerbated by deletion of FGF21. Mechanistically, FGF21 inhibits the activity of CK2α and promotes the degradation of GLI2. In conclusion, these results indicate that FGF21 attenuates skin fibrosis through the CK2α/GLI2 signaling pathway and therefore may be a potential therapeutic target for systemic sclerosis.</div></div>\",\"PeriodicalId\":16311,\"journal\":{\"name\":\"Journal of Investigative Dermatology\",\"volume\":\"145 4\",\"pages\":\"Pages 842-853.e8\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2024-09-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Investigative Dermatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0022202X2402058X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Investigative Dermatology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022202X2402058X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
FGF21 Ameliorates Fibroblasts Activation and Systemic Sclerosis by Inhibiting CK2α/GLI2 Signaling Axis
Systemic sclerosis is a typical fibrotic disease of unknown etiology that is characterized by abnormal fibroblast activation and excessive deposition of extracellular matrix. Unfortunately, effective therapeutic approaches are lacking. FGF21 plays a key role in mediating a variety of biological activities. However, its specific function in systemic sclerosis is unclear. In this study, we found that the expression of FGF21 was significantly downregulated in fibrotic skin tissue and in TGF-β–stimulated fibroblasts. Furthermore, our studies demonstrated that treatment with recombinant FGF21 in the skin significantly alleviated bleomycin-induced and TBRI-activated fibrosis and inhibited the activation of fibroblasts, whereas skin fibrosis was exacerbated by deletion of FGF21. Mechanistically, FGF21 inhibits the activity of CK2α and promotes the degradation of GLI2. In conclusion, these results indicate that FGF21 attenuates skin fibrosis through the CK2α/GLI2 signaling pathway and therefore may be a potential therapeutic target for systemic sclerosis.
期刊介绍:
Journal of Investigative Dermatology (JID) publishes reports describing original research on all aspects of cutaneous biology and skin disease. Topics include biochemistry, biophysics, carcinogenesis, cell regulation, clinical research, development, embryology, epidemiology and other population-based research, extracellular matrix, genetics, immunology, melanocyte biology, microbiology, molecular and cell biology, pathology, percutaneous absorption, pharmacology, photobiology, physiology, skin structure, and wound healing