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 Cthrc1 -/- 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 Cthrc1 -/- 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.

中文翻译：

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含有胶原蛋白三螺旋重复序列-1 通过在体内诱导相邻微血管网络重建来促进汗腺的功能恢复。

背景 汗腺（SGs）在严重烧伤或创伤后具有较低的再生潜力，其再生或功能恢复仍面临许多障碍。在实践中，恢复 SG 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。胶原蛋白三螺旋重复序列-1 (CTHRC1) 首次在血管修复中被发现，越来越多的报告显示皮肤附件规格、模式和再生之间存在密切相关性。本研究的目的是阐明 CTHRC1 在 SG 及其邻近微血管中的作用，并找到恢复 SG 功能的治疗策略。方法首先使用汗液试验、激光多普勒成像、组织清除技术和转录组分析。通过细胞增殖、DiI 标记的乙酰化低密度脂蛋白摄取、管形成和细胞间连接建立测定，进一步探索了 CTHRC1 对真皮微血管内皮细胞 (DMEC) 的影响。通过将蛋白质补充到 Cthrc1 -/- 小鼠的爪子中，最终证实了 CTHRC1 对 SG 功能恢复的影响。结果CTHRC1是小鼠SG功能的关键调节因子。在组织水平上，Cthrc1 缺失导致 SGs 周围微血管网络的紊乱和减少。在分子水平上，Cthrc1 的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，CTHRC1 给药通过诱导邻近血管网络重建显着增强了 SG 功能。结论 CTHRC1 促进 SGs 及其邻近脉管系统的发育、形态发生和功能执行。我们的研究为体内 SG 功能的恢复或再生提供了一个新的靶点。