Urolithin A Promotes Angiogenesis and Tissue Regeneration in a Full-Thickness Cutaneous Wound Model

Zhen-Hua Feng; Jia Chen; Pu-Tao Yuan; Zhong-Yin Ji; Si-Yue Tao; Lin Zheng; Xiao-An Wei; Ze-Yu Zheng; Bing-Jie Zheng; Bin Chen; Jian Chen; Feng-Dong Zhao

doi:10.3389/fphar.2022.806284

Urolithin A Promotes Angiogenesis and Tissue Regeneration in a Full-Thickness Cutaneous Wound Model

Front Pharmacol. 2022 Mar 14:13:806284. doi: 10.3389/fphar.2022.806284. eCollection 2022.

Authors

Zhen-Hua Feng^{1

2}, Jia Chen^{1

2}, Pu-Tao Yuan^{1

2}, Zhong-Yin Ji^{1

2}, Si-Yue Tao^{1

2}, Lin Zheng^{1

2}, Xiao-An Wei^{1

2}, Ze-Yu Zheng^{1

2}, Bing-Jie Zheng^{1

2}, Bin Chen³, Jian Chen^{1

2}, Feng-Dong Zhao^{1

2}

Affiliations

¹ Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou, China.
³ Department of Orthopedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.

Abstract

The treatment of chronic wound is an important topic of current clinical issue. Neovascularization plays a crucial role in skin wound healing by delivering fresh nutrients and oxygen to the wound area. The aim of this study was to investigate the mechanisms of urolithin A (UA) in angiogenesis during wound healing. The results of in vitro experiments showed that treatment with UA (5-20 μM) promoted the proliferation, migration, and angiogenic capacity of HUVECs. Furthermore, we investigated the effect of UA in vivo using a full-thickness skin wound model. Subsequently, we found that UA promoted the regeneration of new blood vessels, which is consistent with the results of accelerated angiogenesis in vitro experiments. After UA treatment, the blood vessels in the wound are rapidly formed, and the deposition and remodeling process of the collagen matrix is also accelerated, which ultimately promotes the effective wound healing. Mechanistic studies have shown that UA promotes angiogenesis by inhibiting the PI3K/AKT pathway. Our study provides evidence that UA can promote angiogenesis and skin regeneration in chronic wounds, especially ischemic wounds.

Keywords: PI3K/AKT pathway; angiogenesis; docking; urolithin A; wound healing.