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Collagen triple helix repeat containing-1 promotes functional recovery of sweat glands by inducing adjacent microvascular network reconstruction in vivo

引用

Burns & Trauma 2022年第1期10卷 387-400页

作者： Xingyu Yuan Xianlan Duan Zhao Li Bin Yao Enhejirigala Wei Song Yi Kong Yuzhen Wang Fanliang Zhang Liting Liang Shijun Zhu Mengde Zhang Chao Zhang Sha Huang Xiaobing Fu School of Medicine Nankai University94 Wei Jin RoadTianjin 300071PR China Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department PLA General Hospital28 Fu Xing RoadBeijing 100853PR China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and RegenerationChinese PLA General Hospital and PLA Medical College51 Fu Cheng RoadBeijing 100048PR China Research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048PR China Academy of Medical Engineering and Translational Medicine Tianjin University92 Weijin RoadTianjin300072PR China College of Graduate Tianjin Medical UniversityTianjin 300070PR China Institute of Basic Medical Research Inner Mongolia Medical UniversityHohhot 010110Inner MongoliaPR China Department of Burn and Plastic Surgery Air Force Hospital of Chinese PLA Central Theater CommandDatong 037000ShanxiPR China

Background:Sweat glands(SGs)have low regenerative potential after severe burns or trauma and their regeneration or functional recovery still faces many obstacles.In practice,restoring SG function requires not only the structural integrity of the gland itself,but also its neighboring tissues,especially blood vessels.Collagen triple helix repeat containing-1(CTHRC1)was first identified in vascular repair,and increasing reports showed a close correlation between cutaneous appendage specification,patterning and regeneration.The purpose of the present study was to clarify the role of CTHRC1 in SGs and their adjacent microvessels and find therapeutic strategies to restore SG function.Methods:The SGs and their adjacent microvascular network of Cthrc^(1−/−)mice were first inves-tigated using sweat test,laser Doppler imaging,tissue clearing technique and transcriptome analysis.The effects of CTHRC1 on dermal microvascular endothelial cells(DMECs)were further explored with cell proliferation,DiI-labeled acetylated low-density lipoprotein uptake,tube for-mation and intercellular junction establishment assays.The effects of CTHRC1 on SG function restoration were finally confirmed by replenishing the protein into the paws of Cthrc(1−/−)mice.Results:CTHRC1 is a key regulator of SG function in mice.At the tissue level,Cthrc1 deletion resulted in the disorder and reduction of the microvascular network around SGs.At the molecular level,the knockout of Cthrc1 reduced the expression of vascular development genes and functional proteins in the dermal tissues.Furthermore,CTHRC1 administration considerably enhanced SG function by inducing adjacent vascular network reconstruction.Conclusions:CTHRC1 promotes the development,morphogenesis and function execution of SGs and their neighboring vasculature.Our study provides a novel target for the restoration or regeneration of SG function in vivo.

关键词： Collagen triple helix repeat containing-1 Sweat glands Microvascular network dermalmicrovascular endothelial cells Reconstruction

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