Parathyroid hormone-related protein production by normal human keratinocytes in vitro.

Parathyroid hormone-related protein production by normal human keratinocytes in vitro.
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正常人角质形成细胞在体外产生甲状旁腺激素相关蛋白质。

DOI:
10.1006/excr.1993.1223
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发表时间:
1993
影响因子:
3.7
通讯作者:
Rosol,TJ
Rosol,TJ
中科院分区:
医学3区
文献类型:
--
作者:
Werkmeister,JR;Merryman,JI;McCauley,LK;Horton,JE;Capen,CC;Rosol,TJ

文献摘要

被引文献

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甲状旁腺激素相关蛋白(PTHrP)在正常表皮生理中的作用及其调控目前尚不清楚。最近的证据表明,PTHrP的产生可能与角质形成细胞在体外的分化程度有关。本研究描述了正常人包皮角质形成细胞(NHFK)在体外自发分化和诱导分化过程中PTHrP的产生。用人PTHrP(1-36)的N末端放射免疫法测定角质形成细胞无血清条件培养液中PTHrP的生成。已知的刺激(钙,1,25-二羟基维生素D3)或抑制(转化生长因子-β)角质形成细胞分化的药物被检测其改变甲状旁腺素rP产生的能力。通过对培养细胞数量和总蛋白含量的测定,证实了这些药物对角质形成细胞生长和分化的影响。细胞融合后,对照细胞(0.08 mM低钙条件下)甲状旁腺素(PTHrP)产量减少,总蛋白含量增加(P<0.01)。角质形成细胞培养液中加入1mM钙可增加细胞数和总蛋白含量(P&lt;0.05),但抑制甲状旁腺素(PTHrP)的产生(P&lt;0.01)。1,25-二羟基维生素D3(10 NM)对细胞数和甲状旁腺素产量无显著影响,但增加了总蛋白的含量(P&lt;0.05)。转化生长因子-β(5 ng/ml)使细胞数减少(P&lt;0.05),总蛋白含量减少(P&lt;0.01),但显著促进甲状旁腺素的产生(P&lt;0.01)。这些数据表明,在体外自发分化和钙诱导分化过程中,NHFK对甲状旁腺素rP的生成均有抑制作用,而转化生长因子-β抑制了正常角质形成细胞的分化,上调了甲状旁腺素的生成。
The role of parathyroid hormone-related protein (PTHrP) and its regulation in normal epidermal physiology is not currently known. Recent evidence suggests that PTHrP production may be related to the degree of differentiation of keratinocytesin vitro. This investigation characterized the production of PTHrP by normal human foreskin keratinocytes (NHFK) during both spontaneously occurring and induced differentiationin vitro. PTHrP production in keratinocyte serum-free conditioned medium was determined using an N-terminal radioimmunoassay for human PTHrP (1-36). Agents known to stimulate (calcium, 1,25-dihydroxyvitamin D3) or inhibit (transforming growth factor-β) keratinocyte differentiation were examined for their ability to alter production of PTHrP. Measurements of cell number and involucrin content of the cultures were made to confirm the effects of these agents on keratinocyte growth and differentiation. The production of PTHrP in control cultures (under low calcium conditions, 0.08 mM) was decreased and involucrin content increased (P< 0.01) after the cells became confluent. The addition of 1 mMcalcium to keratinocyte medium increased cell number and involucrin content of the cultures (P< 0.05) but inhibited production of PTHrP (P< 0.01). The 1,25-dihydroxyvitamin D3(10 nM) had no significant effect on cell number or PTHrP production, but increased involucrin content (P< 0.05). Transforming growth factor-β (5 ng/ml) decreased both cell number (P< 0.05) and involucrin content (P< 0.01), but significantly stimulated PTHrP production (P< 0.01). These data indicate that the production of PTHrP by NHFK is inhibited with the onset of both spontaneously occurring and calcium-induced differentiationin vitro, while transforming growth factor-β-inhibited differentiation and upregulated PTHrP production in normal human keratinocytes.