Morroniside promotes skin wound re-epithelialization by facilitating epidermal stem cell proliferation through GLP-1R-mediated upregulation ofβ-catenin expression  

作　　者：Chenghao Yu Siyuan Yu Zuohua Liu Lei Xu Zhiqiang Zhang Jiaming Wan Pengxiang Ji Ping Zhang Yi Fu Yingying Le Ruixing Hou 

机构地区：[1]Suzhou Ruihua Orthopedic Hospital,Suzhou Medical College of Soochow University,Suzhou 215104,China [2]Department of Hand Surgery,Suzhou Ruihua Orthopedic Hospital,Suzhou 215104,China [3]Yangzhou University Medical College,Yangzhou 225009,China [4]Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China [5]Department of Human Anatomy,Histology and Embryology,School of Biology and Basic Medical Sciences,Suzhou Medical College of Soochow University,Suzhou 215123,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第7期1072-1084,共13页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Suzhou Science and Technology Development Plan(Nos.SKY2023107,and SKY2023108);the Suzhou Municipal Science and Technology Bureau(No.SKJY2021022).

摘　　要：Epidermal stem cells(EpSCs)play a vital role in skin wound healing through re-epithelialization.Identifying chemicals that can promote EpSC proliferation is helpful for treating skin wounds.This study investigates the effect of morroniside on cutaneous wound healing in mice and explores the underlying mechanisms.Application of 10‒50μg/mL of morroniside to the skin wound promotes wound healing in mice.In vitro studies demonstrate that morroniside stimulates the proliferation of mouse and human EpSCs in a time-and dose-dependent manner.Mechanistic studies reveal that morroniside promotes the proliferation of EpSCs by facilitating the cell cycle transition from the G1 to S phase.Morroniside increases the expression ofβ-catenin via the glucagon-like peptide-1 receptor(GLP-1R)-mediated PKA,PKA/PI3K/AKT and PKA/ERK signaling pathways,resulting in an increase in cyclin D1 and cyclin E1 expression,either directly or by upregulating c-Myc expression.This process ultimately leads to EpSC proliferation.Administration of morroniside to mouse skin wounds increases the phosphorylation of AKT and ERK,the expressions ofβ-catenin,c-Myc,cyclin D1,and cyclin E1,as well as the proliferation of EpSCs,in periwound skin tissue,and accelerates wound re-epithelialization.These effects of morroniside are mediated by the GLP-1R.Overall,these results indicate that morroniside promotes skin wound healing by stimulating the proliferation of EpSCs via increasingβ-catenin expression and subsequently upregulating c-Myc,cyclin D1,and cyclin E1 expressions through GLP-1R signaling pathways.Morroniside has clinical potential for treating skin wounds.

关 键 词：MORRONISIDE wound healing epidermal stem cells cell proliferation glucagon-like peptide-1 receptor Β-CATENIN 

分 类 号：R62[医药卫生—整形外科] Q5[医药卫生—外科学]