The purpose of this study is to present a novel strategy to enhance
collagen production in cells. To identify
amino acid analogs with excellent
collagen production-enhancing effects, human dermal fibroblasts (HDFs) were treated with 20 kinds of amidated
amino acids and 20 kinds of free
amino acids, individually at 1 mM. The results showed that
glycinamide enhanced
collagen production (secreted
collagen level) most effectively.
Glycine also enhanced
collagen production to a lesser degree. However, other
glycine derivatives, such as N-acetyl
glycine, N-acetyl
glycinamide,
glycine methyl ester,
glycine ethyl ester, and
glycyl glycine, did not show such effects.
Glycinamide increased type I and III
collagen protein levels without affecting COL1A1 and COL3A1
mRNA levels, whereas transforming growth factor-β1 (TGF-β1, 10 ng mL-1) increased both
mRNA and
protein levels of
collagens.
Ascorbic acid (AA, 1 mM) increased COL1A1 and COL3A1
mRNA and
collagen I
protein levels. Unlike TGF-β1, AA and
glycinamide did not increase the
protein level of α-smooth muscle actin, a marker of differentiation of fibroblasts into myofibroblasts. The combination of AA and
glycinamide synergistically enhanced
collagen production and
wound closure in HDFs to a level similar to that in cells treated with TGF-β1. AA derivatives, such as
magnesium ascorbyl 3-phosphate (MAP),
3-O-ethyl ascorbic acid, ascorbyl 2-O-glucoside, and ascorbyl tetraisopalmitate, enhanced
collagen production, and the
mRNA and
protein levels of
collagens at 1 mM, and their effects were further enhanced when co-treated with
glycinamide. Among AA derivatives, MAP had a similar effect to AA in enhancing
wound closure, and its effect was further enhanced by
glycinamide. Other AA derivatives had different effects on
wound closure. This study provides a new strategy to enhance cell
collagen production and wound healing using
glycinamide in combination with AA.