Enhanced Type I Collagen Synthesis in Fibroblasts by Dermal Stem/Progenitor Cell-Derived Exosomes

The self-duplication and differentiation of dermal stem cells are essential for the maintenance of dermal homeostasis. Fibroblasts are derived from dermal stem cells and produce components of connective tissue, such as collagen, which maintains the structure of the dermis. Cell-cell communication is required for the maintenance of tissue homeostasis, and the role of exosomes in this process has recently been attracting increasing attention. Dermal stem cells and fibroblasts have been suggested to communicate with each other in the dermis; however, the underlying mechanisms remain unclear. In the present study, we investigated communication between dermal stem/progenitor cells (DSPCs) and fibroblasts via exosomes. We collected exosomes from DSPCs and added them to a culture of fibroblasts. With the exosomes, COL1A1 mRNA expression was up-regulated and dependent on the Akt phosphorylation. Exosomes collected from fibroblasts did not show the significant up-regulation of COL1A1 mRNA expression. We then performed a proteomic analysis and detected 74 proteins specific to DSPC-derived exosomes, including ANP32B related to Akt phosphorylation. We added exosomes in which ANP32B was knocked down to a fibroblast culture and observed neither Akt phosphorylation nor enhanced type I collagen synthesis. Additionally, an immunohistochemical analysis of skin tissues revealed that ANP32B expression levels in CD271-positive dermal stem cells were lower in old subjects than in young subjects. These results suggest that DSPCs promote type I collagen synthesis in fibroblasts by secreting exosomes containing ANP32B, which may contribute to the maintenance of skin homeostasis; however, this function of DSPCs may decrease with aging.