The role of Hrd1 in ultraviolet (UV) radiation induced photoaging.
Yi Jin, Xianye Cheng, Xin Huang, Fan Ding, Sae Rom Lee, Fengdi Wang, Xiaoyi Lu, Dongming Su, Bin Chen
Author Information
Yi Jin: Department of Dermatology and Venereology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Xianye Cheng: Department of Dermatology and Venereology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Xin Huang: Department of Pediatric and Preventive Dentistry, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, China.
Fan Ding: Department of Dermatology and Venereology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Sae Rom Lee: Department of Dermatology and Venereology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Fengdi Wang: Department of Dermatology and Venereology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Xiaoyi Lu: Department of Dermatology and Venereology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Dongming Su: Center of Metabolic Disease Research, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Bin Chen: Department of Dermatology and Venereology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
The purpose of the present study was to evaluate the role of Hrd1 in the ultraviolet (UV) radiation induced photoaging and explore its potential mechanism. The nude mice were exposed to the UVA/UVB irradiation for 10 weeks. The animals were subcutaneously injected with AAV5-NC, Hrd1-shRNA-AAV5, or Hrd1-overexpression-AAV5. The HSF cells were also transfected with Ad-NC, Ad-shRNA-Hrd1, or Ad-Hrd1, and irradiated by UVA/UVB stimulation. The clinical skin samples were harvested for detecting Hrd1 and IGF-1R expressions. As a result, the knockdown of Hrd1 attenuated the histopathological alteration and collagen degradation in UV-induced nude mice. The inhibition of Hrd1 by Hrd1-shRNA-AAV5 and Ad-shRNA-Hrd1 inhibited the Hrd1 expression and promoted IGF-1R, Type I collagen and type III collagen in mice and HSF cells. The overexpression of Hrd1 exerted the reverse effect. The Co-IP assay also indicated the interaction between Hrd1 and IGF-1R. Hrd1-mediated IGF-1R downregulation and collagen degradation were also observed in clinical skin samples. In conclusion, the present results demonstrated that Hrd1 degraded IGF-1R and collagen formation in UV-induced photoaging.