Purinergic receptors are part of a functional signaling system for proliferation and differentiation of human epidermal keratinocytes

Purinergic receptors are part of a functional signaling system for proliferation and differentiation of human epidermal keratinocytes
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DOI:
10.1046/j.1523-1747.2003.12261.x
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发表时间:
2003-06-01
影响因子:
6.5
通讯作者:
Burnstock, G
Burnstock, G
中科院分区:
医学1区
文献类型:
--
作者:
Greig, AVH;Linge, C;Burnstock, G

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我们研究了正常人表皮中 P2X(5)、P2X(7)、P2Y(1) 和 P2Y(2) 受体亚型的表达及其与增殖标记物(PCNA 和 Ki-67)、角质形成细胞分化(细胞角蛋白 K10 和外皮蛋白)和凋亡标记物(TUNEL 和 antiaspase-3)的关系。使用免疫组织化学,我们发现四种受体中的每一种都在表皮的空间不同区域中表达,表明这些受体具有不同的功能作用。对人角质形成细胞的原代培养物和移植的大鼠皮肤进行功能研究,其中将不同的 P2 受体亚型激动剂和拮抗剂分别应用于培养的角质形成细胞或皮下注射到皮肤中。细胞数量的增加是由低剂量的非特异性 P2 受体激动剂 ATP、P2Y(2) 受体激动剂 UTP 引起的(p
We investigated the expression of P2X(5), P2X(7), P2Y(1) and P2Y(2) receptor subtypes in normal human epidermis and in relation to markers of proliferation (PCNA and Ki-67), keratinocyte differentiation (cytokeratin K10 and involucrin) and markers of apoptosis (TUNEL and anticaspase-3). Using immunohistochemistry, we showed that each of the four receptors was expressed in a spatially distinct zone of the epidermis, suggesting different functional roles for these receptors. Functional studies were performed on primary cultures of human keratinocytes and on explanted rat skin, where different P2 receptor subtype agonists and antagonists were applied to cultured keratinocytes or injected subcutaneously into the skin, respectively. An increase in cell number was caused by low doses of the nonspecific P2 receptor agonist ATP, the P2Y(2) receptor agonist UTP (p