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USP15 Maintains TGF-β Pathway Activity by Deubiquitinating TBR1 in Wound Healing

24 Pages Posted: 26 Sep 2018

See all articles by Yi-Xuan Zhao

Yi-Xuan Zhao

Shanghai Jiao Tong University (SJTU), School of Medicine, Shanghai 9th People's Hospital, Department of Plastic & Reconstructive Surgery

Zi Wang

Shanghai Jiao Tong University (SJTU), School of Medicine, Shanghai 9th People's Hospital, Department of Plastic & Reconstructive Surgery

Chia-Kang Ho

Shanghai Jiao Tong University (SJTU), School of Medicine, Shanghai 9th People's Hospital, Department of Plastic & Reconstructive Surgery

Guo-You Zhang

Shanghai Jiao Tong University (SJTU), School of Medicine, Shanghai 9th People's Hospital, Department of Plastic & Reconstructive Surgery

Qing-Feng Li

Shanghai Jiao Tong University (SJTU), School of Medicine, Shanghai 9th People's Hospital, Department of Plastic & Reconstructive Surgery

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Abstract

Wound healing is a process of cutaneous barrier reconstruction after skin injury that involves diversified cytokines and cells. Ubiquitin-specific peptidase 15 (USP15), similar to several deubiquitinating enzymes (DUBs), can remove ubiquitin chains from specific proteins to rescue them from degradation. However, the regulatory role of USP15 in wound healing remains unclear. Here, our research aimed to investigate the dynamic function of USP15 in wound healing. First, in USP15 knockout mice, we observed a significant delay in wound closure. In addition, inhibition of cell proliferation and migration was observed in USP15-silenced human dermal fibroblasts (HDFs). Through RNA sequencing, we revealed that the transforming growth factor-β (TGF-β) pathway was suppressed after USP15 knockdown. Furthermore, coimmunoprecipitation (Co-IP) demonstrated that USP15 could interact with the TGF-β receptor I (TBR1) and promote its deubiquitination, thereby maintaining TGF-β signalling pathway activity by enhancing TBR1 stability. Conclusively, these observations shed light on the function and mechanisms of USP15 modulation of the TGF-β signalling pathway in wound healing, thus providing a novel potential target for the treatment of refractory wounds.

Funding Statement: This work was supported in part by the following grants: The National Natural Science Foundation of China (81571904 to G-Y, Zhang, 81620108019 to Q-F, Li) and the Project Sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (201550005 to G-Y, Zhang).

Declaration of Interests: The authors state no conflict of interest.

Ethics Approval Statement: All animals were cared for and used in accordance with the appropriate guidance procedures. The protocol received ethical approval from the Independent Ethics Committee of Shanghai Ninth People's Hospital.

Keywords: wound healing; USP15; deubiquitination; TGF-β; TBR1

Suggested Citation

Zhao, Yi-Xuan and Wang, Zi and Ho, Chia-Kang and Zhang, Guo-You and Li, Qing-Feng, USP15 Maintains TGF-β Pathway Activity by Deubiquitinating TBR1 in Wound Healing (September 9, 2018). Available at SSRN: https://ssrn.com/abstract=3247869

Yi-Xuan Zhao

Shanghai Jiao Tong University (SJTU), School of Medicine, Shanghai 9th People's Hospital, Department of Plastic & Reconstructive Surgery

China

Zi Wang

Shanghai Jiao Tong University (SJTU), School of Medicine, Shanghai 9th People's Hospital, Department of Plastic & Reconstructive Surgery

China

Chia-Kang Ho

Shanghai Jiao Tong University (SJTU), School of Medicine, Shanghai 9th People's Hospital, Department of Plastic & Reconstructive Surgery

China

Guo-You Zhang

Shanghai Jiao Tong University (SJTU), School of Medicine, Shanghai 9th People's Hospital, Department of Plastic & Reconstructive Surgery

China

Qing-Feng Li (Contact Author)

Shanghai Jiao Tong University (SJTU), School of Medicine, Shanghai 9th People's Hospital, Department of Plastic & Reconstructive Surgery

China

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