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

被引：9

作者：

Feng, Zhen-hua ^{[1
,2
]}

Chen, Jia ^{[1
,2
]}

Yuan, Pu-tao ^{[1
,2
]}

Ji, Zhong-yin ^{[1
,2
]}

Tao, Si-yue ^{[1
,2
]}

Zheng, Lin ^{[1
,2
]}

Wei, Xiao-an ^{[1
,2
]}

Zheng, Ze-yu ^{[1
,2
]}

Zheng, Bing-jie ^{[1
,2
]}

Chen, Bin ^{[3
]}

Chen, Jian ^{[1
,2
]}

Zhao, Feng-dong ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Orthopaed Surg, Hangzhou, Peoples R China

[2] Key Lab Musculoskeletal Syst Degenerat & Regenera, Hangzhou, Peoples R China

[3] Jiaxing Univ, Dept Orthoped, Affiliated Hosp 2, Jiaxing, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2022年 / 13卷

基金：

中国国家自然科学基金;

关键词：

urolithin A; wound healing; PI3K; AKT pathway; angiogenesis; docking; GROWTH-FACTOR; CELLS; APOPTOSIS; PROTECTS; PATHWAY; STRESS; CANCER; SIGNAL; AMPK;

D O I：

10.3389/fphar.2022.806284

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 mu M) 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.

引用

页数：10

共 37 条

[1] Vascularization strategies for skin tissue engineering [J].

Amirsadeghi, Armin ;

Jafari, Arman ;

Eggermont, Loek J. ;

Hashemi, Seyedeh-Sara ;

Bencherif, Sidi A. ;

Khorram, Mohammad .

BIOMATERIALS SCIENCE, 2020, 8 (15) :4073-4094

[2] Growth factors in the treatment of diabetic foot ulcers [J].

Bennett, SP ;

Griffiths, GD ;

Schor, AM ;

Leese, GP ;

Schor, SL .

BRITISH JOURNAL OF SURGERY, 2003, 90 (02) :133-146

[3] Nitrite Anion Therapy Protects Against Chronic Ischemic Tissue Injury in db/db Diabetic Mice in a NO/VEGF-Dependent Manner [J].

Bir, Shyamal C. ;

Pattillo, Christopher B. ;

Pardue, Sibile ;

Kolluru, Gopi K. ;

Shen, Xinggui ;

Giordano, Tony ;

Kevil, Christopher G. .

DIABETES, 2014, 63 (01) :270-281

[4] Mechanism of Sustained Release of Vascular Endothelial Growth Factor in Accelerating Experimental Diabetic Healing [J].

Brem, Harold ;

Kodra, Arber ;

Golinko, Michael S. ;

Entero, Hyacinth ;

Stojadinovic, Olivera ;

Wang, Vincent M. ;

Sheahan, Claudia M. ;

Weinberg, Alan D. ;

Woo, Savio L. C. ;

Ehrlich, H. Paul ;

Tomic-Canic, Marjana .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2009, 129 (09) :2275-2287

[5] Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing [J].

Castilho, R. M. ;

Squarize, C. H. ;

Gutkind, J. S. .

ORAL DISEASES, 2013, 19 (06) :551-558

[6] Urolithin A Inhibits Epithelial-Mesenchymal Transition in Lung Cancer Cells via P53-Mdm2-Snail Pathway [J].

Cheng, Feng ;

Dou, Jintao ;

Zhang, Yong ;

Wang, Xiang ;

Wei, Huijun ;

Zhang, Zhijian ;

Cao, Yuxiang ;

Wu, Zhihao .

ONCOTARGETS AND THERAPY, 2021, 14 :3199-3208

[7] Dhcr24 activates the PI3K/Akt/HKII pathway and protects against dilated cardiomyopathy in mice [J].

Dong, Wei ;

Guan, Fei-fei ;

Zhang, Xu ;

Gao, Shan ;

Liu, Ning ;

Chen, Wei ;

Zhang, Lian-feng ;

Lu, Dan .

ANIMAL MODELS AND EXPERIMENTAL MEDICINE, 2018, 1 (01) :40-52

[8] RETRACTED: Paeoniflorin promotes angiogenesis and tissue regeneration in a full-thickness cutaneous wound model through the PI3K/AKT pathway (Retracted article. See vol. 237, pg. 2303, 2022) [J].

Dong, Xiaoyu ;

He, Zili ;

Xiang, Guangheng ;

Cai, Leyi ;

Xu, Zhenjiang ;

Mao, Cong ;

Feng, Yongzeng .

JOURNAL OF CELLULAR PHYSIOLOGY, 2020, 235 (12) :9933-9945

[9] Chronic Venous Insufficiency [J].

Eberhardt, Robert T. ;

Raffetto, Joseph D. .

CIRCULATION, 2014, 130 (04) :333-346

[10] Urolithin A induces cell cycle arrest and apoptosis by inhibiting Bcl-2, increasing p53-p21 proteins and reactive oxygen species production in colorectal cancer cells [J].

El-Wetidy, Mohammad S. ;

Ahmad, Rehan ;

Rady, Islam ;

Helal, Hamed ;

Rady, Mohamad I. ;

Vaali-Mohammed, Mansoor-Ali ;

Al-Khayal, Khayal ;

Traiki, Thamer Bin ;

Abdulla, Maha-Hamadien .

CELL STRESS & CHAPERONES, 2021, 26 (03) :473-493

← 1 2 3 4 →