Tong P S, Horowitz N N, Wheeler L A
Department of Biological Sciences, Discovery Research, Allergan, Inc./Herbert Laboratories, Irvine, California.
J Invest Dermatol. 1990 Jan;94(1):126-31. doi: 10.1111/1523-1747.ep12873985.
Retinoids have been shown to either stimulate or inhibit epidermal keratinocyte proliferation. We have observed that in serum and growth factor free medium (basal medium), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) stimulated DNA synthesis in mouse epidermal keratinocyte cultures (mKC) in a time- and dose-dependent manner. Incubation with all-trans retinoic acid (RA) greatly enhanced the stimulatory effect of EGF. Transforming growth factor beta (TGF beta) inhibited the EGF-induced DNA synthesis in a dose-dependent manner, and the inhibition was greatly enhanced by a low dose of RA. Treatment of growth-factor deprived human keratinocyte cultures (hKC) with RA before incubation in basal medium containing EGF or a mixture of EGF, bovine pituitary extract (BPE), and insulin caused a dose-related increase in DNA synthesis and cell growth (cell number), respectively. A low concentration of RA also enhanced the inhibitory effect of TGF beta on growth-factor-induced DNA synthesis and cell growth in hKC. These findings suggest that the differential effects of retinoids on epidermal keratinocyte proliferation are in part due to an enhancement of the response of keratinocytes to positive and negative peptide growth factors.
维甲酸已被证明可刺激或抑制表皮角质形成细胞的增殖。我们观察到，在无血清和生长因子的培养基（基础培养基）中，表皮生长因子（EGF）和转化生长因子α（TGFα）能以时间和剂量依赖的方式刺激小鼠表皮角质形成细胞培养物（mKC）中的DNA合成。用全反式维甲酸（RA）孵育可大大增强EGF的刺激作用。转化生长因子β（TGFβ）以剂量依赖的方式抑制EGF诱导的DNA合成，低剂量的RA可大大增强这种抑制作用。在用含EGF或EGF、牛垂体提取物（BPE）和胰岛素混合物的基础培养基孵育之前，先用RA处理生长因子缺乏的人角质形成细胞培养物（hKC），可分别导致DNA合成和细胞生长（细胞数量）呈剂量相关增加。低浓度的RA也增强了TGFβ对hKC中生长因子诱导的DNA合成和细胞生长的抑制作用。这些发现表明，维甲酸对表皮角质形成细胞增殖的不同作用部分归因于角质形成细胞对正负肽生长因子反应的增强。
