Notch1 在真皮多潜能细胞抗皮肤光老化中的作用机制

How to delay photo-aging of skin becomes a research hotspot all around the world, especially the mechanism of protecting skin from photo-aging. Our team have already found out transplanted DMCs could increase the thickness and the content of collagenⅠ in mouse dermis, but“How” is still a question. The paracrine of DMCs maybe play an important role in tissue regeneration and repair besides proliferation and differentiation. Notch1 signal pathway is indispensible in many signals of wound healing, the results above were published already. Our research will figure out how concentrated supernatant of DMCs protect FBs and mouse model from UVA, explore the mode and regulation mechanism of Notch signal pathway in protection from photo-aging of skin. Our research will work on molecular, cell, animal level, try to clarify the change of paracrine of DMCs and Notch signal, find out the clinical meaning of them. Our study can help discover the cells and pathways of protection of skin photo-aging, establish the base of turning the result from laboratory into treatment in clinic.

如何延缓皮肤光老化已成为国内外皮肤科学的研究热点，明确光老化的机制尤为重要。本课题组以往的研究表明移植真皮多潜能细胞（DMCs）能够增加小鼠真皮厚度和真皮中Ⅰ型胶原纤维的表达,但具体机制仍不明确。皮肤光老化的修复中, DMCs除了定向分化成修复组织的特定细胞外,其旁分泌作用也是诱导组织再生修复的关键。而Notch1信号已被证明在皮肤修复的多条信号通路中不可或缺(以上相关成果已发表SCI论文)。本项目拟探讨DMCs浓缩上清对UVA照射成纤维细胞及光老化小鼠模型的保护作用, 并通过激活和抑制Notch1信号，明确其在此保护作用中的角色和调节机制。本项目将在分子、细胞、动物三个层次展开，并通过分子机制研究进行纵向的突破。揭示DMCs及其旁分泌与Notch1信号在光老化相关临床问题的关系。帮助我们揭示预防、治疗光老化有关的细胞及通路，并为发现的相关靶点应用于转化医学奠定理论基础。

皮肤光老化是国内外皮肤科学的研究热点，明确光老化的机制尤为重要。真皮多潜能细胞（DMCs）在皮肤光老化修复中，除定向分化成修复组织的特定细胞外,其旁分泌作用也是诱导组织再生修复的关键，Notch 信号通路中，其受体与配体通过局部细胞间的相互作用来广泛调节脊 椎和非脊椎动物的胚胎及成年个体的发育和内环境稳定。我们已经证实，DMCs旁分泌可有效改善中波紫外线UVB对皮肤成纤维细胞造成的紫外损伤，且此过程与Notch信号通路密切相关。本研究利用成年小鼠原代皮肤成纤维细胞建立光老化模型，并加入DMCs培养上清，研究其对光老化模型细胞功能学及分子水平的变化，阐明Notch信号通路在光老化修复过程中的作用，为光老化治疗提供依据和治疗靶点。