Sano Masahiro, Shang Yi, Nakane Akio, Saito Tomoaki
a Aomori Prefectural Industrial Technology Research Center , Hirosaki Industrial Research Institute , Hirosaki , Japan.
b Department of Microbiology and Immunology , Hirosaki University Graduate School of Medicine , Hirosaki , Japan.
Biosci Biotechnol Biochem. 2017 Jul;81(7):1379-1385. doi: 10.1080/09168451.2017.1318695. Epub 2017 May 2.
Proteoglycan (PG) is a heavily glycosylated protein, localized to cell surface and extracellular matrix, and has various functions. Recently, it has been gradually revealed that PG interacts with various growth factors and morphogens and regulates cellular functions. Although salmon nasal cartilage PG (Salmon-PG) increases proliferation of immortalized cells, its mechanism remains unclear. In this study, we confirmed the effect of Salmon-PG on normal human dermal fibroblast (NHDF) and investigated the mechanism of PG action on NHDF. Salmon-PG dose- and time-dependently increased NHDF proliferation. Receptor tyrosine kinase array revealed that Salmon-PG increased only Erk1/2 signaling. Erk1/2 phosphorylation was significantly increased by Salmon-PG in a time-(10 min) and dose-(400 or 800 μg/mL) dependent manner. MEK inhibitor suppressed the enhancement of NHDF proliferation by Salmon-PG. The overall findings indicate that Salmon-PG plays a role as a growth factor in NHDF via Erk1/2 activation, suggesting that Salmon-PG contributes to the maintenance of skin homeostasis.
蛋白聚糖（PG）是一种高度糖基化的蛋白质，定位于细胞表面和细胞外基质，具有多种功能。最近，逐渐发现PG与多种生长因子和形态发生素相互作用并调节细胞功能。尽管鲑鱼鼻软骨蛋白聚糖（Salmon-PG）可增加永生化细胞的增殖，但其机制仍不清楚。在本研究中，我们证实了Salmon-PG对正常人皮肤成纤维细胞（NHDF）的作用，并研究了PG对NHDF的作用机制。Salmon-PG以剂量和时间依赖性方式增加NHDF的增殖。受体酪氨酸激酶阵列显示，Salmon-PG仅增加Erk1/2信号传导。Salmon-PG以时间（10分钟）和剂量（400或800μg/mL）依赖性方式显著增加Erk1/2磷酸化。MEK抑制剂可抑制Salmon-PG对NHDF增殖的增强作用。总体研究结果表明，Salmon-PG通过激活Erk1/2在NHDF中发挥生长因子的作用，提示Salmon-PG有助于维持皮肤稳态。
