Delayed Wound Healing In Usp15 Knockout Mice
Yixuan Zhao, Guo-You Zhang, Qing-Feng Li.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital,Shanghai Jiaotong University， School of Medicine, Shanghai, China.
DELAYED WOUND HEALING IN UBIQUITIN-SPECIFIC PROTEASE-15 KNOCKOUT MICE Background: Ubiquitin-specific protease-15 (USP15), which belongs to deubiquitylating enzyme family, has been found involved in transforming growth factor-beta/SMAD (TGF-β/SMAD) signaling pathway by combining SMAD7 and deubiquitination TGFβ Receptor I (TBR1). However, its role in wound repair remains unclear. Methods: In this research, USP15 knockout (USP15-KO) mice were applied and full excisional wounds were created on the dorsal skin of both USP15-KO and wild type (WT) mice. Results: General view and hematoxylin-eosin (HE) results revealed that USP15-KO mice displayed an impaired wound closure rate compared with WT mice (p<0.05). Immunochemistry showed that USP15-KO mice exhibited less collagen but thicker normal skin than WT mice (p<0.05). In addition, USP15-KO mice trended to present a low expression level of TGF-β1 and TBR1 compared with WT (p<0.05). Consistent with lower migration ability of USP15-KO mice epidermal cells, scratch and transwell assay in vitro respectively proved that Hacat cells and human dermal fibroblasts (HDF) transfected with USP15-siRNAs were significantly less motile than control. Meanwhile, G0/G1 cell cycle arrest was detected in Hacat cells after knocking down Usp15. Moreover, USP15-siRNA interfered Hacat cells presented depression of plasminogen activator inhibitor-1 (PAI-1) and TBR1 protein as well as low expression of TGF-β1 mRNA. Conclusions: These findings indicate that USP15 plays as a novel regulator both in vivo and in vitro via TGF-β1 signaling pathway and might be a potential therapeutic target in cutaneous wound healing.
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