TSH Receptor and Thyroid-Specific Gene Expression in Human Skin
TSH Receptor and Thyroid-Specific Gene Expression in Human Skin
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DOI：
10.1038/jid.2009.180
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发表时间：
2010-01-01
影响因子：
6.5
通讯作者：
D'Armiento, Massimino
中科院分区：
文献类型：
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作者：
Cianfarani, Francesca;Baldini, Enke;D'Armiento, Massimino
实验证据表明，在自身免疫性甲状腺疾病（AITDs）中，皮肤是针对甲状腺特异性抗原的自身抗体的靶标；然而，这些自身抗体在皮肤改变中的作用尚不清楚。为了深入了解皮肤中名义上甲状腺特异性基因的功能，我们分析了促甲状腺激素受体（TSH-R）、甲状腺球蛋白（Tg）、碘化钠同调体（NIS）和甲状腺过氧化物酶（TPO）基因在正常人皮肤活检组织和培养的原代角质形成细胞和真皮成纤维细胞中的表达。结果显示皮肤活检中存在所有转录本。然而，在角质形成细胞和成纤维细胞中，只检测到TSH-R信使RNA。皮肤标本的Western blot和免疫组化分析证实，在角质形成细胞和成纤维细胞中存在TSH-R蛋白。此外，TSH处理诱导培养的角质形成细胞和成纤维细胞增殖，并增加角质形成细胞胞内cAMP。最后，从Graves病（而非慢性淋巴细胞性甲状腺炎）患者血清中亲和纯化的igg刺激了培养的角化细胞中cAMP的积累及其增殖。总之，培养的角质形成细胞和成纤维细胞中甲状腺特异性基因的表达以及TSH和igg对这些细胞的有丝分裂作用支持了针对甲状腺特异性抗原的自身抗体可能有助于AITDs皮肤症状的概念。
Experimental evidence suggests that in autoimmune thyroid diseases (AITDs) the skin is a target of autoantibodies against thyroid-specific antigens; however, the role of these autoantibodies in skin alterations remains unclear. To gain insight into the function of nominally thyroid-specific genes in skin, we analyzed the expression of thyroid-stimulating hormone-receptor (TSH-R), thyroglobulin (Tg), sodium iodide symporter (NIS), and thyroperoxidase (TPO) genes in normal human skin biopsies and cultured primary keratinocytes and dermal fibroblasts. The results revealed the presence of all the transcripts in skin biopsies. However, in keratinocytes and fibroblasts, only TSH-R messenger RNA was always detected. Western blot and immunohistochemical analyses of skin specimens confirmed the presence of TSH-R protein in keratinocytes and fibroblasts. Moreover, TSH treatment induced the proliferation of cultured keratinocytes and fibroblasts and increased keratinocyte intracellular cAMP. Finally, affinity-purified IgGs from serum of patients affected by Graves' disease, but not by chronic lymphocytic thyroiditis, stimulated cAMP accumulation in cultured keratinocytes, as well as their proliferation. In conclusion, the expression of thyroid-specific genes in cultured keratinocytes and fibroblasts and the mitogenic effects of TSH and IgGs on these cells support the concept that autoantibodies against thyroid-specific antigens may contribute to cutaneous symptoms in AITDs.