1,25-Dihydroxyvitamin D production and receptor binding in human keratinocytes varies with differentiation.
1,25-Dihydroxyvitamin D production and receptor binding in human keratinocytes varies with differentiation.
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DOI：
10.1016/s0021-9258(18)60729-x
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发表时间：
1988-04
期刊：
影响因子：
--
通讯作者：
S. Pillai;D. Bikle;P. Elias
中科院分区：
文献类型：
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作者：
S. Pillai;D. Bikle;P. Elias
培养的人包皮角质形成细胞从25-羟基胆钙化醇（25-（OH）D3）产生1，25-二羟基胆钙化醇（1，25-（OH）2D 3）和24，25-二羟基胆钙化醇（24，25-（OH）2D 3）。由这些细胞产生的1，25-（OH）2D 3与分化的早期事件相关，如转氨酶活性的表达和皮层包膜的前体蛋白，外皮蛋白的水平。相反，24，25-（OH）2D 3产量的增加，随着1，25-（OH）2D 3产量的下降，与终末分化标记，皮层包膜形成相关。外源性1，25-（OH）_2D_3（10（-11）-10（-9）M）在这些细胞生长的所有阶段抑制1-α-羟化酶。培养的角质形成细胞表达1，25-（OH）2D 3受体，其在蔗糖密度梯度中具有与鸡肠胞质溶胶受体相似的沉降行为。生长早期阶段的细胞（汇合前和汇合）比汇合后细胞含有更高数量的受体（26-27 fmol/mg蛋白质）。这些受体对1，25-（OH）2D 3的解离常数（237-278 pM）并不因分化而一致地改变。由于1，25-（OH）2D 3是包括表皮在内的各种系统中细胞分化的有效刺激物，我们的结果表明内源性1，25-（OH）2D 3产生可能参与培养中的角质形成细胞的分化，并且可能参与体内的分化。
Human foreskin keratinocytes in culture produce 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) and 24,25-dihydroxycholecalciferol (24,25-(OH)2D3) from 25-hydroxycholecalciferol (25-(OH)D3). The production of 1,25-(OH)2D3 by these cells correlated with the early events of differentiation such as expression of transglutaminase activity and the levels of a precursor protein for the cornified envelopes, involucrin. In contrast, the increased production of 24,25-(OH)2D3, as 1,25-(OH)2D3 production declined, correlated with the terminal differentiation marker, cornified envelope formation. Exogenous 1,25-(OH)2D3 (10(-11)-10(-9) M) inhibited the 1-alpha-hydroxylase at all stages of growth of these cells. Keratinocytes in culture expressed receptors for 1,25-(OH)2D3 which had similar sedimentation behavior in sucrose density gradients as chick intestinal cytosol receptors. Cells in early stages of growth (preconfluent and confluent) contained higher numbers of receptors (26-27 fmol/mg protein) than post-confluent cells. The dissociation constant (237-278 pM) of these receptors for 1,25-(OH)2D3 was not consistently altered by differentiation. Since 1,25-(OH)2D3 is a potent stimulator of cell differentiation in a variety of systems including the epidermis, our results suggest the possibility that endogenous 1,25-(OH)2D3 production may participate in the differentiation of keratinocytes in culture and, perhaps, in vivo.