Peptide TK-HR from the Skin of Chinese Folk Medicine Frog Hoplobatrachus Rugulosus Accelerates Wound Healing via the Activation of the Neurokinin-1 Receptor

被引：2

作者：

Wu, Jiena ^{[1
]}

Xiong, Weichen ^{[1
]}

Li, Jinqiao ^{[1
]}

Liao, Hang ^{[1
]}

Chai, Jinwei ^{[1
]}

Huang, Xiaowen ^{[2
]}

Lai, Shian ^{[3
]}

Kozlov, Sergey ^{[4
]}

Chu, Xinwei ^{[5
]}

Xu, Xueqing ^{[1
]}

机构：

[1] Southern Med Univ, Sch Pharmaceut Sci, NMPA Key Lab Res & Evaluat Drug Metab, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China

[2] Southern Med Univ, Nanfang Hosp, Dept Dermatol, Guangzhou 510515, Guangdong, Peoples R China

[3] Doshisha Univ, Fac Sci & Engn, Dept Mol Chem & Biochem, Kyotanabe, Kyoto 6100394, Japan

[4] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Ul Miklukho Maklaya 16-10, Moscow 117997, Russia

[5] Southern Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, 1838 N Guangzhou Ave, Guangzhou 510515, Guangdong, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 66卷 / 23期

基金：

中国国家自然科学基金;

关键词：

NEUROPEPTIDE SUBSTANCE-P; TREE FROG; MACROPHAGES; MOUSE; INFLAMMATION; CHEMOKINES;

D O I：

10.1021/acs.jmedchem.3c01434

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Wound healing is a complex process and remains a considerable challenge in clinical trials due to the lack of ideal therapeutic drugs. Here, a new peptide TK-HR identified from the skin of the frog Hoplobatrachus rugulosus was tested for its ability to heal cutaneous wounds in mice. Topical application of TK-HR at doses of 50-200 mu g/mL significantly accelerated wound closure without causing any adverse effects in the animals. In vitro and in vivo investigations proved the regulatory role of the peptide on neutrophils, macrophages, keratinocytes, and vein endothelial cells involved in the inflammatory, proliferative, and remodeling phases of wound healing. Notably, TK-HR activated the MAPK and TGF-beta-Smad signaling pathways by acting on NK1R in RAW264.7 cells and mice. The current work has identified that TK-HR is a potent wound healing regulator that can be applied for the treatment of wounds, including diabetic foot ulcers and infected wounds, in the future.

引用

页码：16002 / 16017

页数：16