The skin seems to rejuvenate upon exposure to factors within the circulation of young organisms. Intrinsic factors that modulate skin aging are poorly understood. We used heterochronic parabiosis and aptamer-based proteomics to identify serum-derived rejuvenating factors. We discovered a novel extracellular function of hyaluronan and proteoglycan link protein 1 (HAPLN1). Its serum levels decreased with age, disturbing the integrity of the skin extracellular matrix, which is predominantly composed of collagen I and hyaluronan; levels of various markers, which decrease in aged skin, were significantly restored and by the administration of recombinant human HAPLN1 (rhHAPLN1). rhHAPLN1 protected transforming growth factor beta receptor 2 on the cell surface from endocytic degradation via mechanisms such as regulation of viscoelasticity, CD44 clustering. Moreover, rhHAPLN1 regulated the levels of nuclear factor erythroid 2–related factor 2, phosphorylated nuclear factor kappa B, and some cyclin-dependent kinase inhibitors such as p16 and p21. Therefore, rhHAPLN1 may act as a novel biomechanical signaling protein to rejuvenate aged skin.

中文翻译：

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透明质酸和蛋白聚糖连接蛋白 1 – 一种使老化皮肤恢复活力的新型信号分子


接触年轻有机体循环中的因素后，皮肤似乎会恢复活力。人们对调节皮肤衰老的内在因素知之甚少。我们使用异时联体共生和基于适体的蛋白质组学来鉴定血清来源的恢复活力因子。我们发现了透明质酸和蛋白聚糖连接蛋白 1 (HAPLN1) 的一种新的细胞外功能。它的血清水平随着年龄的增长而下降，扰乱了皮肤细胞外基质的完整性，该基质主要由 I 型胶原蛋白和透明质酸组成；通过施用重组人 HAPLN1 (rhHAPLN1)，老化皮肤中降低的各种标记物的水平得到显着恢复。 rhHAPLN1 通过粘弹性调节、CD44 聚集等机制保护细胞表面的转化生长因子 β 受体 2 免受内吞降解。此外，rhHAPLN1 调节核因子红细胞 2 相关因子 2、磷酸化核因子 kappa B 和一些细胞周期蛋白依赖性激酶抑制剂（如 p16 和 p21）的水平。因此，rhHAPLN1可能作为一种新型生物力学信号蛋白来使老化皮肤恢复活力。