Injury-induced interleukin-1 alpha promotes Lgr5 hair follicle stem cells de novo regeneration and proliferation via regulating regenerative microenvironment in mice

Inflammation and Regeneration

Research Article

Mulan Qahar¹  Edward E. Tredget²  Jiayi Qiu³  Zhimeng Fan⁴  Guang Yang⁵  Yaojiong Wu⁶  Weiwei Chu⁶  Haiyan Chen⁷  Qun Chen⁷ 

[1] Department of Burn and Plastic Surgery, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, 518035, Shenzhen, China;Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University, 518055, Shenzhen, China;Department of Surgery, Division of Critical Care, University of Alberta Hospital, ABT6G2B7, Edmonton, AB, Canada;Faculté Des Lettres, Sorbonne Université (Paris Sorbonne, 75006, Paris IV), Paris, France;State Key Laboratory of Chemical Oncogenomics, and the Institute of Biopharmaceutical and Health Engineering (iBHE), Shenzhen International Graduate School, Tsinghua University, 518055, Shenzhen, China;State Key Laboratory of Chemical Oncogenomics, and the Institute of Biopharmaceutical and Health Engineering (iBHE), Shenzhen International Graduate School, Tsinghua University, 518055, Shenzhen, China;Department of Burn and Plastic Surgery, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, 518035, Shenzhen, China;Division of Nephrology, Peking University Shenzhen Hospital, 518036, Shenzhen, China;State Key Laboratory of Chemical Oncogenomics, and the Institute of Biopharmaceutical and Health Engineering (iBHE), Shenzhen International Graduate School, Tsinghua University, 518055, Shenzhen, China;Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University, 518055, Shenzhen, China;Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University, 518055, Shenzhen, China;

关键词: Hair follicles;    Lgr5 stem cells;    Interleukin-1alpha;    Wound healing;    Regeneration;    HaCaT;    SKPs;   

DOI  :  10.1186/s41232-023-00265-7

 received in 2022-09-26, accepted in 2023-01-29,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe hair follicles (HFs) are barely regenerated after loss in injuries in mammals as well as in human beings. Recent studies have shown that the regenerative ability of HFs is age-related; however, the relationship between this phenomenon and the stem cell niche remains unclear. This study aimed to find a key secretory protein that promotes the HFs regeneration in the regenerative microenvironment.MethodsTo explore why age affects HFs de novo regeneration, we established an age-dependent HFs regeneration model in leucine-rich repeat G protein-coupled receptor 5 (Lgr5) + /mTmG mice. Proteins in tissue fluids were analyzed by high-throughput sequencing. The role and mechanism of candidate proteins in HFs de novo regeneration and hair follicle stem cells (HFSCs) activation were investigated through in vivo experiments. The effects of candidate proteins on skin cell populations were investigated by cellular experiments.ResultsMice under 3-week-old (3W) could regenerate HFs and Lgr5 HFSCs, which were highly correlated with the immune cells, cytokines, IL-17 signaling pathway, and IL-1α level in the regeneration microenvironment. Additionally, IL-1α injection induced de novo regeneration of HFs and Lgr5 HFSCs in 3W mouse model with a 5 mm wound, as well as promoted activation and proliferation of Lgr5 HFSCs in 7-week-old (7W) mice without wound. Dexamethasone and TEMPOL inhibited the effects of IL-1α. Moreover, IL-1α increased skin thickness and promoted the proliferation of human epidermal keratinocyte line (HaCaT) and skin-derived precursors (SKPs) in vivo and in vitro, respectively.ConclusionsIn conclusion, injury-induced IL-1α promotes HFs regeneration by modulating inflammatory cells and oxidative stress-induced Lgr5 HFSCs regeneration as well as promoting skin cell populations proliferation. This study uncovers the underlying molecular mechanisms enabling HFs de novo regeneration in an age-dependent model.

【 授权许可】

CC BY   
© The Author(s) 2023

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