2022, Vol. 26 ›› Issue (25): 3993-3998

Expression of leptin receptor in mouse skin and the role of leptin receptor-positive cells in skin development and wound healing

Wang Ao, Chu Hongshang, Wu Hongguang, Li Ke, Liu Huijuan   

Abstract: BACKGROUND: It is believed that leptin receptor (LepR) marks the adult bone marrow mesenchymal stem cells in mice and LepR+ cells contribute to the regeneration of fractured bone. However, the residence of LepR+ stromal cells in skin and the function of the population in skin development and repair are poorly understood.  
OBJECTIVE: To investigate the expression of LepR in mouse skin and the role of LepR+ cells in development and tissue repair.
METHODS:   The study was approved by the Experimental Animal Ethics and Use Committee of Shanghai Jiao Tong University with the approval No. 1504002. The LepR-Cre; tdTomato mice were generated by using the classic Cre-loxP system for tracing the expression of LepR in mouse skin. Flow cytometry was used to analyze surface markers on Tomato+ cells. A full-thickness skin excision wound model was constructed on the back of LepR-Cre; tdTomato mice to trace the distribution of LepR+ cells in skin wound healing. The LepR-Cre; Tsc1fl/fl mice for specific deletion of Tsc1 in LepR+ cells were constructed to identify the role of Tsc1 in mouse skin development.  
RESULTS AND CONCLUSION: (1) LepR was expressed in dermal papilla, stroma, and dermal white adipose tissue in mice skin. (2) Immunofluorescence staining revealed that LepR+ cells partially co-expressed with stromal marker Vimentin and adipocyte marker Perilipin. Cell surface marker analysis showed that LepR lineage cells were negative for CD11b, CD45, and CD31, and positive for CD73 and Sca-1. LepR labeled a population of mesenchymal stem cells in mouse skin. (3) Punching experiment of LepR-Cre; tdTomato mice uncovered that LepR+ cells were involved in injury repair. (4) The LepR-Cre; Tsc1fl/fl mice presented the phenotype that the thickness of dermis and dermal white adipose tissue increased and the number of adipocytes increased significantly. It is concluded that LepR is expressed in mouse skin and cells of the LepR lineage in the skin are involved in tissue development and damage repair.
Key words: LepR lineage tracing, mesenchymal stem cells, skin, dermis, dermal white adipose tissue, development, wound healing, Tsc1