Protective Mechanism of Adipose-Derived Stem Cells in Remodelling of the Skin Stem Cell Niche during Photoaging ;

Abstract

Background/Aims: Skin photoaging is primarily caused by the functional attrition of skin stem cells. The skin stem cell niche plays an important role in maintaining stem cell survival and behaviour. In our study, we hypothesized that UVB irradiation induces skin photoaging by changing skin stem cell niches and that transferred adipose-derived stem cells (ADSCs) can remodel the niches by affecting the BMP signalling pathway and transdifferentiating into skin stem cells. Methods: Sixty-four C57BL/6J mice were divided into the following groups: a control group, the UVB group and the UVB+ADSCs group. Western blot assays, immunofluorescence analysis and real-time PCR were used to measure differences in the expression of niche components among the three groups. Furthermore, we tested whether transplanted ADSCs express skin stem cell markers, such as p63, α6-integrin and CD34. Results: The expression levels of Bmp4, its downstream factors Smad1 and MAPK1 and a regulatory factor of the niche, i.e., NFATc1, were lower in the UVB group than were those in the control group (P< 0.05) but higher in the UVB+ADSCs group than were those in the UVB group (P< 0.05). Compared with Bmp4, Nanog (a downstream factor of Bmp4), and MMP13 (a regulatory factor of the niche), ICAM-1 (a proinflammatory gene), p63 (a basal transcription factor), β1-integrin, Mtnr1a and Tyr (melanogenesis-related factors) showed the opposite expression trends (P< 0.05). Bmp2 and Collagen IV levels did not significantly change among the three groups (P> 0.05). Skin stem cell markers, such as p63, α6-integrin and CD34, were coexpressed in the ADSCs, which suggested the ADSCs may transdifferentiate into skin stem cells. Conclusion: We found that UVB irradiation results in typical photoaging signs by altering skin stem cell niches and that Bmp4 was a key factor in BMP signalling in hair follicles. ADSCs reversed these typical photoaging signs by remodelling skin stem cell niches through BMP4 pathway modulation and transdifferentiation into skin stem cells.