Yuan Xingyu, Duan Xianlan, Li Zhao, Yao Bin, Song Wei, Kong Yi, Wang Yuzhen, Zhang Fanliang, Liang Liting, Zhu Shijun, Zhang Mengde, Zhang Chao, Huang Sha, Fu Xiaobing
School of Medicine, Nankai University, 94 Wei Jin Road, Tianjin 300071, PR China.
Research Center for Tissue Repair and Regeneration affiliated to the Medical Innovation Research Department, PLA General Hospital, 28 Fu Xing Road, Beijing 100853, PR China.
Burns Trauma. 2022 Aug 2;10:tkac035. doi: 10.1093/burnst/tkac035. eCollection 2022.
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.
The SGs and their adjacent microvascular network of mice were first investigated 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 formation and intercellular junction establishment assays. The effects of CTHRC1 on SG function restoration were finally confirmed by replenishing the protein into the paws of mice.
CTHRC1 is a key regulator of SG function in mice. At the tissue level, deletion resulted in the disorder and reduction of the microvascular network around SGs. At the molecular level, the knockout of 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.
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 .
汗腺（SGs）在严重烧伤或创伤后再生潜力较低，其再生或功能恢复仍面临诸多障碍。在实际应用中，恢复汗腺功能不仅需要腺体本身的结构完整性，还需要其邻近组织，尤其是血管。含胶原蛋白三螺旋重复序列-1（CTHRC1）最初是在血管修复中被发现的，越来越多的报道表明其与皮肤附属器的特化、模式形成和再生密切相关。本研究的目的是阐明CTHRC1在汗腺及其相邻微血管中的作用，并寻找恢复汗腺功能的治疗策略。
首先使用汗液测试、激光多普勒成像、组织透明技术和转录组分析对小鼠的汗腺及其相邻微血管网络进行研究。通过细胞增殖、DiI标记的乙酰化低密度脂蛋白摄取、管腔形成和细胞间连接建立实验，进一步探究CTHRC1对真皮微血管内皮细胞（DMECs）的影响。最后通过向小鼠爪部补充该蛋白，证实CTHRC1对汗腺功能恢复的影响。
CTHRC1是小鼠汗腺功能的关键调节因子。在组织水平上，CTHRC1缺失导致汗腺周围微血管网络紊乱和减少。在分子水平上，CTHRC1基因敲除降低了真皮组织中血管发育基因和功能蛋白的表达。此外，给予CTHRC1可通过诱导相邻血管网络重建，显著增强汗腺功能。
CTHRC1促进汗腺及其邻近脉管系统的发育、形态发生和功能执行。我们的研究为汗腺功能的恢复或再生提供了一个新的靶点。
