小分子Forskolin诱导成纤维细胞重编程为血管内皮细胞及抗瘢促皮肤愈合的研究

Perfect skin healing after trauma is a hot spot and difficulty in the field of regenerative medicine research. Pathological healing after trauma not only affects appearance but also causes dysfunction, mental disorder and hypertrophic scars. Compared with traditional wound treatments, the small compound Forskolin, which is sustained by the silk protein carrier, has the advantages of low cost, quick and long effect. Recent studies suggest that 1 Forskolin activates endogenous oxidative stress related pathways to inhibit local inflammatory responses. 2 The effect of Forskolin to promote wound healing and suppress the scar in animal models is obvious..The microenvironment changes after trauma can be induced mature myofibroblasts reprogramming of epidermal stem cells. 3 In the post-traumatic microenvironment mature myofibroblasts can be induced differentiated into vascular endothelial cells to promoting wound vascularization by Forskolin. It is expected that small molecule Forskolin regulated cell reprogramming is closely related to tissue repair and regeneration. Therefore, this project plans to study the mechanism of Forskolin on cell reprogramming from materials, cells, molecules and animal models. About the transgenic mice in animal experiment, we’ll use endogenous tracing technology to confirm that the small molecule intervention micro environment by trauma is linked with dermal fibroblasts reprogramming. It achieves effective clinical interventions on regeneration of post-traumatic multiple adnexal.

皮肤创伤后的完美愈合是再生医学领域的研究热点和难点。创伤后的病理性愈合不仅影响外观而且造成功能障碍、精神障碍以及增生性瘢痕。与传统创面治疗相比，本项目采用蚕丝蛋白载体缓释小分子化合物给药，具有成本低、实效长等优点。新近研究提示：1小分子Forskolin激活内源性氧化应激相关通路抑制局部炎症反应；2小分子化合物Forskolin在动物模型中抗瘢促愈合疗效显著；3在创伤后的微环境下，小分子Forskolin诱导已分化成熟的肌成纤维细胞重编程为血管内皮细胞进而促进创面血管化。可预期：此小分子调控的细胞重编程与创周的组织修复与再生有紧密联系。因此本项目计划从细胞、分子水平探讨小分子Forskolin引发的细胞重编程的机制解析，并在动物水平，利用转基因小鼠进行内源性示踪，证实小分子干预后形成的创伤微环境下真皮成纤维细胞重编程为血管内皮细胞，为实现创伤后多种附属器的再生提供有效的临床干预手段。

创伤修复是再生医学的重要分支，提高皮肤及附属器的再生修复是创伤修复领域的热点和难点。本项目利用小分子化合物FSK作用于创伤局部，通过改变损伤局部的微循环，调节皮肤组成中的关键修复细胞成纤维细胞，将其重编程为血管内皮细胞进而促进创面的血管化愈合。本研究通过体内体外的实验，完成成纤维细胞的重编程和转分化，达到血管的再生修复，加速创面的完美愈合，同时这一结果的取得也为多种血管再生障碍性疾病提供了新的研究思路和临床用药指导。