Proteoglycan (PG) is heavily glycosylated protein, localizes 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. In the previous study, we found that salmon nasal cartilage PG (Salmon-PG) increases NHDF proliferation via Erk1/2 activation. Furthermore, to enhance the effect of Salmon-PG on biological function, we created the various modified Salmon-PG and investigated the effects on normal human dermal fibroblast (NHDF). Exp.1: To compare the effect of native and modified Salmon-PG on biological function, we investigated the effect of modified Salmon-PG on the proliferation of NHDF. Modified Salmon-PG does-dependently increased NHDF proliferation and its effect was higher than those of native Salmon-PG. Exp.2: Since we found that Salmon-PG increases NHDF proliferation via Erk1/2 activation in the previous study, we examined the effect of modified Salmon-PG on Erk1/2 phosphorylation by western blot analysis. The modified Salmon-PG (50, 100, 200, 400, 800 and 1600μg/ml) significantly increased Erk1/2 phosphorylation of NHDF compared with native salmon-PG. Exp.3: We analyzed whether the effect of modified Salmon-PG on the cell proliferation of NHDF is mediated through the Erk1/2 signal pathway. MEK inhibitor suppressed the enhancement of NHDF proliferation by modified Salmon-PG. The overall findings indicate that modified Salmon-PG plays a role as a stronger growth factor in NHDF via Erk1/2 activation than native Salmon-PG, suggesting that modified Salmon-PG strongly contributes to the maintenance of skin homeostasis.