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CCN1 Protein Promotes Mechanical-Stretch-Induced Skin Regeneration by Activating Epithelial-Mesenchymal Transition

30 Pages Posted: 6 Aug 2018

See all articles by Yiwen Zhou

Yiwen Zhou

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

Haizhou Li

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

Xiao Liang

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

Hengyu Du

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

Yinjun So

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

Hao Chen

Guangdong University of Technology, Guangzhou Higher Education Mega Center, Institute of Biomedical and Pharmaceutical Sciences

Zhichao Wang

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

Wenhui Liu

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

Rui Jin

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

Bangda Chai

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

Ran Duan

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

Xiaolu Huang

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

Qingfeng Li

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

More...

Abstract

In clinical practice, mechanical stretch is widely used to regenerate skin for soft-tissue reconstruction, which is termed skin expansion. However, the ability of stretch-induced skin regeneration is limited and searching for ways to enhance the expansion efficacy is a major challenge. Here, we found that expression of the CCN family member 1 (CCN1) gene, also known as cysteine-rich angiogenic inducer 61 (CYR61), was elevated in expanded skin of both humans and rats, along with enhanced epithelial-mesenchymal transition (EMT). In vitro studies suggested that CCN1 could promote cell proliferation and prevent cell apoptosis, as well as inducing EMT directly in keratinocytes. In vivo studies elucidated that CCN1 protein could facilitate dedifferentiation of the epidermis and promote skin regeneration by activating EMT in rats. Furthermore, CCN1 protein was found to significantly increase the flap thickness, improve the blood supply and restore the structure in a rat model of skin expansion. In conclusion, our findings demonstrate that CCN1-induced EMT is a crucial event in mechanical-stretch-induced skin regeneration and that CCN1 may serve as a potential therapeutic target to promote skin regeneration and enhance the efficacy of skin expansion.
Funding: This work was supported by grants from the National Natural Science Foundation of China (No. 81501668, No. 81620108019 and No. 81230042).
Declaration of Interests: The authors have no financial interest to declare in relation to the content of this article.
Ethics Approval Statement: Written informed consent for sample collection was obtained from patients, and sample collection was approved by the Ethics Committee of Shanghai Ninth People’s Hospital (Shanghai, China).

Keywords: Mechanical stretch; Skin regeneration; EMT; CCN1; Cyr61

Suggested Citation

Zhou, Yiwen and Li, Haizhou and Liang, Xiao and Du, Hengyu and So, Yinjun and Chen, Hao and Wang, Zhichao and Liu, Wenhui and Jin, Rui and Chai, Bangda and Duan, Ran and Huang, Xiaolu and Li, Qingfeng, CCN1 Protein Promotes Mechanical-Stretch-Induced Skin Regeneration by Activating Epithelial-Mesenchymal Transition (February 7, 2018). Available at SSRN: https://ssrn.com/abstract=3207898

Yiwen Zhou

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

Shanghai
China

Haizhou Li

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

Shanghai
China

Xiao Liang

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

Shanghai
China

Hengyu Du

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

Shanghai
China

Yinjun So

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

Shanghai
China

Hao Chen

Guangdong University of Technology, Guangzhou Higher Education Mega Center, Institute of Biomedical and Pharmaceutical Sciences

China

Zhichao Wang

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

Shanghai
China

Wenhui Liu

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

Shanghai
China

Rui Jin

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

Shanghai
China

Bangda Chai

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

Shanghai
China

Ran Duan

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

Shanghai
China

Xiaolu Huang

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

Shanghai
China

Qingfeng Li (Contact Author)

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

Shanghai
China

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