Tranexamic acid inhibits melanogenesis partially via stimulation of TGF‐β1 expression in human epidermal keratinocytes
Tranexamic acid inhibits melanogenesis partially via stimulation of TGF‐β1 expression in human epidermal keratinocytes
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DOI：
10.1111/exd.14509
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发表时间：
2021-12
影响因子：
3.6
通讯作者：
X. Xing;Zhongyi Xu;Li Chen;Shanglin Jin;Chengfeng Zhang;L. Xiang
中科院分区：
文献类型：
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作者：
X. Xing;Zhongyi Xu;Li Chen;Shanglin Jin;Chengfeng Zhang;L. Xiang
口服氨甲环酸（TA）是治疗黄褐斑的有效药物，但作用机制尚不清楚。本研究旨在通过调节角质形成细胞中TGF - β1的表达来证明TA对黑色素形成的影响。我们首先测定了TGF - β1在TA处理的角质细胞条件培养基（KCM）中的表达水平。然后，通过RT - PCR和western blot分析，检测TA处理的KCM存在时，人表皮黑色素细胞（nhem）中小眼症相关转录因子（MITF）、酪氨酸酶（TYR）和酪氨酸酶相关蛋白1 （TRP - 1）的mRNA和蛋白水平。测定黑色素含量和酪氨酸酶活性。TGF‐β1基因在角质形成细胞中被小干扰RNA （siRNA）敲低。经TA处理后，角质形成细胞中TGF - β1 mRNA和蛋白水平显著升高。在经TA处理的KCM存在下，nhm中黑色素含量、酪氨酸酶活性、TYR、MITF和TRP‐1的蛋白和mRNA水平均下调。在角质形成细胞中敲低TGF - β1可以减弱TA处理的KCM对黑色素生成的抑制作用。TA可以刺激角质形成细胞中TGF - β1的表达，通过旁分泌信号进一步抑制黑色素生成。
Oral tranexamic acid (TA) has been an effective treatment for melasma with unclear mechanism. The present study aimed to demonstrate the effect of TA on melanogenesis via regulation of TGF‐β1 expression in keratinocytes. We firstly determined the expression level of TGF‐β1 in TA‐treated keratinocyte‐conditioned medium (KCM). Then, the mRNA and protein levels of microphthalmia‐associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase‐related protein 1 (TRP‐1) of human epidermal melanocytes (NHEMs) in the presence of TA‐treated KCM were evaluated via RT‐PCR and western blot analysis. Moreover, melanin content and tyrosinase activity were quantified. TGF‐β1 gene was knocked down by small interfering RNA (siRNA) in keratinocytes. The mRNA and protein levels of TGF‐β1 in keratinocytes were significantly increased after TA treatment. Melanin contents, tyrosinase activity, protein and mRNA levels of TYR, MITF and TRP‐1 were downregulated in NHEMs in the presence of TA‐treated KCM. Knockdown of TGF‐β1 in keratinocytes could attenuate the inhibitory effect of TA‐treated KCM on melanogenesis. TA could stimulate TGF‐β1 expression in keratinocytes, which further inhibits melanogenesis through the paracrine signalling.