A role for thyroid hormone in wound healing through keratin gene expression

A role for thyroid hormone in wound healing through keratin gene expression
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DOI:
10.1210/en.2003-1696
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发表时间:
2004-05-01
期刊:
影响因子:
4.8
通讯作者:
Holick, MF
Holick, MF
中科院分区:
医学2区
文献类型:
--
作者:
Safer, JD;Crawford, TM;Holick, MF

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甲状腺激素(TH)在伤口愈合中的重要性尚不清楚。为了获得洞察力,我们评估了TH缺乏对培养的角质形成细胞中伤口愈合基因的影响。RT-PCR法显示,角蛋白6a(K6a)和角蛋白16(K16)基因在TH缺失细胞中的表达分别是TH缺失细胞的3.8%(P&0.005)和1.90倍(P<0.05)。实时定量聚合酶链式反应显示,K6a、K16和K17的完整细胞表达水平分别为18-(P<0.001)、10-(P<0.001)和4倍(P<0.005)。为了检验对最佳伤口愈合的要求,我们对比了TH缺陷小鼠和IP T-3处理的小鼠。伤后4天,ip T-3治疗的小鼠伤口闭合程度是甲状腺功能减退小鼠的两倍(P<0.001)。反转录-聚合酶链式反应显示,K6a和K17基因在正常小鼠皮肤中的表达分别是甲减小鼠皮肤的5倍(P&0.001)和1.7倍(P<0.05)。T-3对于角质形成细胞的增殖是必需的,而角质形成细胞是最佳伤口愈合所必需的。T-3通过刺激伤口修复角蛋白基因的表达而发挥影响。因此,对于正在接受手术的甲状腺功能减退患者,我们的数据支持围手术期的T-3治疗。
The importance of thyroid hormone (TH) in wound healing is not well understood. To gain insight, we evaluated the impact of TH deficiency on wound-healing genes in cultured keratinocytes. By RT-PCR, keratin 6a (K6a) and 16 (K16) gene expression in TH replete cells was 3.8- (P < 0.005) and 1.9-fold (P < 0.05) greater, respectively, than expression in TH-deficient cells. By real-time PCR, TH replete cell expression of K6a, K16, and K17 was greater than in deficient cells: 18- ( P < 0.001), 10- ( P < 0.001), and 4-fold ( P < 0.005), respectively. To examine TH requirement for optimal wound healing, we contrasted TH-deficient vs. ip T-3-treated mice. Four days after wounding, ip T-3-treated mice had twice the degree of wound closure as hypothyroid mice ( P < 0.001). By RT-PCR, K6a and K17 gene expression from control mouse skin was greater than from hypothyroid mouse skin: 5- ( P < 0.001) and 1.7- fold ( P < 0.05), respectively. T-3 is necessary for the keratinocyte proliferation required for optimal wound healing. T-3 exerts influence by stimulating expression of the wound-healing keratin genes. Thus, for hypothyroid patients undergoing surgery that cannot be delayed until euthyroidism is achieved, our data support T-3 treatment for the perioperative period.