Figure 1.

COL17 as a critical modulator in skin aging. Intrinsic or extrinsic aging leads to genomic instability and then results in decreased COL17 expression and increased COL17 proteolysis, which is regulated by proteases (e.g., MMP9, ADAM9, 10, 17, ELANE) and protease inhibitors (e.g., PAI-1, PAI-2, A1AT, TIMP1, TIMP2, TIMP3). These finally induce epidermis thinning and fragility, and hair greying and loss. For ESCs, COL17 down-regulation leads to the imbalance of SDCs and ADCs through interactions with aPKC and PAR3. For HFSCs, down-regulation of COL17 causes HF miniaturization through Notch and c-MYC signaling. For MSCs, down-regulation of COL17 in ESCs and HFSCs creates a niche with the involvement of TGF-β signaling, leading to MSC aging.