TGF-BETA AND RETINOIC ACID - REGULATORS OF GROWTH AND MODIFIERS OF DIFFERENTIATION IN HUMAN EPIDERMAL-CELLS
TGF-BETA AND RETINOIC ACID - REGULATORS OF GROWTH AND MODIFIERS OF DIFFERENTIATION IN HUMAN EPIDERMAL-CELLS
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DOI：
10.1091/mbc.1.11.791
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发表时间：
1990-10-01
期刊：
影响因子：
--
通讯作者：
FUCHS, E
中科院分区：
文献类型：
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作者：
CHOI, Y;FUCHS, E
在皮肤表皮中，增殖祖细胞和终末分化细胞之间存在着良好的平衡。我们检查了TGF-β和视黄酸（RA）对在保留体内表皮的大多数形态和生化特征的条件下培养的正常和恶性人表皮角质形成细胞中控制这种平衡的影响。我们的结果揭示了 TGF-β 的显着和多效性作用。和 RA 对角质形成细胞的影响。与类维生素A相反，TGF-β作用于有丝分裂活性的基底细胞以延缓细胞增殖。尽管退出细胞周期是进行终末分化的必要先决条件，但TGF-β抑制基底上细胞中的正常角化并促进通常与伤口愈合和表皮过度增殖相关的分化类型。 TGF-β和RA对正常角化的作用是协同的，而对与过度增殖相关的异常分化的作用是拮抗的。这些观察结果强调了这样一个观念：环境变化可以单独作用于群体内细胞的增殖和分化。在此处使用的条件下，TGF-β对人角质形成细胞的作用优于RA，并且TGF-β似乎并未因RA治疗而被诱导。这一发现与 RA 加速而不是抑制筏培养物增殖的事实相一致。总的来说，我们的数据表明，这两个因素对表皮生长和分化的影响是多方面的，并且它们在角质形成细胞中的作用耦合程度可能在不同条件和/或不同物种中有所不同。
In the epidermis of skin, a fine balance exists between proliferating progenitor cells and terminally differentiating cells. We examined the effects of TGF-.beta.s and retinoic acid (RA) on controlling this balance in normal and malignant human epidermal keratinocytes cultured under conditions where most morphological and biochemical features of epidermis in vivo are retained. Our results revealed marked and pleiotropic effects of both TGF-.beta. and RA on keratinocytes. In contrast to retinoids, TGF-.beta.s acted on mitotically active basal cells to retard cell proliferation. Although withdrawal from the cell cycle is a necessary prerequisite for commitment to terminal differentiation, TGF-.beta.s inhibited normal keratinization in suprabasal cells and promoted the type of differentiation commonly associated with wound-healing and epidermal hyperproliferation. The actions of TGF-.beta.s and RA on normal keratinization were synergistic, whereas those on abnormal differentiation associated with hyperproliferation were antagonistic. These observations underscore the notion that environmental changes can act separately on proliferating and differentiating cells within the population. Under the conditions used here, the action of TGF-.beta.s on human keratinocytes was dominant over RA, and TGF-.beta.s did not seem to be induced as a consequence of RA treatment. This finding is consistent with the fact that RA accelerated, rather than inhibited, proliferation in raft cultures. Collectively, our data suggest that the effects of both factors on epidermal growth and differentiation are multifaceted and the extent to which their action is coupled in keratinocytes may vary under different conditions and/or in different species.