Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
Cells. 2022 Nov 24;11(23):3749. doi: 10.3390/cells11233749.
Skin senescence is characterized by a decrease in extracellular matrix and the accumulation of senescent fibroblasts in the dermis, and their secretion of humoral factors. Ependymin-related protein 1 (EPDR1) is involved in abnormal fibroblast metabolism and collagen deposition, however, its relation to skin aging is unclear. We investigated whether and how EPDR1 is involved in age-related dermal deterioration. When young dermal fibroblasts and senescent cells were co-cultured in a semipermeable membrane separation system, the young fibroblasts showed decreased gene expression of collagen type I α1 chain () and elastin, and increased expression of matrix metalloproteinase () and . Senescence marker expression and EPDR1 production were increased in the culture medium of senescent cells. Treatment of young fibroblasts with recombinant EPDR1, enhanced matrix-related gene expression and suppressed expression, whereas knockdown had the opposite effects. EPDR1 gene and protein expression were increased in aged skin, compared to young skin. These results suggest that senescent cells affect nearby fibroblasts, in part through EPDR1 secretion, and exert negative effects on matrix production in the dermis. These results may lead to the discovery of potential candidate targets in the development of skin anti-aging therapies.
皮肤衰老的特征是细胞外基质减少和真皮中衰老成纤维细胞的积累，以及它们分泌的体液因子。类脑啡肽相关蛋白 1（EPDR1）参与异常成纤维细胞代谢和胶原蛋白沉积，但它与皮肤衰老的关系尚不清楚。我们研究了 EPDR1 是否以及如何参与与年龄相关的皮肤恶化。当年轻的真皮成纤维细胞和衰老细胞在半透膜分离系统中共培养时，年轻的成纤维细胞表现出胶原蛋白 I α1 链（）和弹性蛋白的基因表达减少，基质金属蛋白酶（）和增加。衰老细胞培养基中衰老标志物表达和 EPDR1 产生增加。用重组 EPDR1 处理年轻成纤维细胞，增强了基质相关基因的表达，抑制了的表达，而则相反。与年轻皮肤相比，衰老皮肤中 EPDR1 的基因和蛋白表达增加。这些结果表明，衰老细胞通过 EPDR1 的分泌影响附近的成纤维细胞，并对真皮中的基质产生负面影响。这些结果可能为开发皮肤抗衰老疗法提供潜在的候选靶点。
