TSP-1调控SKPs抗光老化TGF-β/Smad信号通路的研究

皮肤前体细胞（SKPs）是从成体皮肤中分离出的一种新型干细胞。近期发现SKPs可通过TGF-β/Smad通路抑制皮肤光老化，为修复光损伤提供了新思路，但因调控机制不清限制其开发应用。血小板反应素-1 (TSP-1)是TGF-β通路的重要激活物之一，我们前期研究发现经紫外线照射后SKPs的TSP-1基因及蛋白表达均增高，推测TSP-1通过调控TGF-β/Smad通路在SKPs抗光老化中发挥关键作用。本课题拟通过基因过表达及RNA干扰技术上调或下调SKPs的TSP-1，观察细胞增殖、凋亡、自噬等生物学特性及UV照射后TGF-β/Smad通路的改变；并将TSP-1改变前后的SKPs移植入动物模型中，检测光老化相关基因和蛋白表达、真皮功能及形态学变化。本项目将在分子、细胞、动物三个层面探索TSP-1对TGF-β/Smad的调控作用，明确SKPs抗光老化的分子机制，为临床开发产品提供新靶位。

Skin-derived precursor cells (SKPs) are a novel category of stem cells attained from adult skin. The recent finding that SKPs are able to suppress skin photoaging via activating transforming growth factor-β (TGF-β)/Smad pathway, sheds light on the new approach to repairing photo damage, but the unclear mechanisms restrict its appliance. Thrombospondin-1 (TSP-1), one of the essential activators of TGF-β pathway, showed higher level of gene and protein expression after being exposed to ultraviolet, observed in our previous research, suggesting TSP-1 may be a key element in SKPs curbing photoaging through controlling TGF-β/Smad pathway. The methodologies of this project are to observe SKPs’ physical features such as proliferation, apoptosis and autophagy, and the changes of TGF-β/Smad pathway after ultraviolet irradiation by up and down-regulating TSP-1 in SKPs with gene overexpression and RNA interference, then to transplant SKPs to animal modules with TSP-1 before and after ultraviolet exposure, detecting the expression of photoaging-associated gene and protein and changes of dermal functions and morphology. By exploring TSP-1’s role in TGF-β/Smad pathway in terms of molecular and cellular biology and animal, this project aims to figure out the molecular mechanisms of SKPs inhibiting photo-damage, identify novel targets for new products to prevent and cure photoaging.