Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor.
Differentiation of human orbital preadipocyte fibroblasts induces expression of functional thyrotropin receptor.
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DOI：
10.1210/jcem.84.7.5838
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发表时间：
1999-07
期刊：
影响因子：
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通讯作者：
R. Valyasevi;Dana Erickson;D. Harteneck;C. Dutton;Armin E. Heufelder;Soma C. Jyonouchi;R. Bahn
中科院分区：
文献类型：
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作者：
R. Valyasevi;Dana Erickson;D. Harteneck;C. Dutton;Armin E. Heufelder;Soma C. Jyonouchi;R. Bahn
虽然已知与Graves‘甲亢相关的自身抗原是TSH受体(TSHR)，但该抗原是否在Graves’眼病(GO)的发病机制中起主要作用尚不清楚。我们试图确定来自眼眶脂肪/结缔组织的成纤维细胞是否能够分化为承载免疫活性和功能性TSHR的脂肪细胞。此外，我们评估了TSHR基因在正常和GO眼眶脂肪/结缔组织标本中的相对表达水平。GO和正常眼眶前脂肪细胞成纤维细胞在已知刺激脂肪细胞分化的条件下培养，显示出脂肪生成的证据和TSHR蛋白的阳性免疫染色。此外，分化后的细胞在TSH刺激下产生的cAMP明显多于来自相同个体细胞的未分化后的细胞。其他研究表明，与正常眼眶组织标本相比，GO中TSHR基因的表达相对更高。这些结果表明，眼眶前脂肪细胞成纤维细胞在分化过程中其TSHR的表达增加，提示这些细胞在GO的发病机制中起重要作用。此外，我们的研究支持TSHR在这种情况下可能是一个重要的靶抗原的概念。GO眼眶内刺激脂肪细胞分化和TSHR表达的因素尚不明确。
Although the autoantigen involved in Graves' hyperthyroidism is known to be the TSH receptor (TSHr), whether this antigen plays a primary role in the pathogenesis of Graves' ophthalmopathy (GO) is unclear. We sought to determine whether fibroblasts derived from orbital adipose/connective tissue are capable of differentiating into adipocytes that bear immunoreactive and functional TSHr. In addition, we assessed relative levels of TSHr gene expression in normal and GO orbital adipose/connective tissue specimens. GO and normal orbital preadipocyte fibroblasts, cultured under conditions known to stimulate adipocyte differentiation, showed evidence of adipogenesis and positive immunostaining for TSHr protein. In addition, significantly more cAMP was produced in response to TSH stimulation in the differentiated cultures than in undifferentiated cultures derived from the same individuals' cells. Other studies demonstrated relatively greater TSHr gene expression in GO than in normal orbital tissue specimens. These results indicate that orbital preadipocyte fibroblasts increase their TSHr expression with differentiation and suggest that these cells play an important role in the pathogenesis of GO. Furthermore, our studies support the concept that TSHr may be an important target antigen in this condition. Factors that stimulate adipocyte differentiation and TSHr expression in the orbit in GO have yet to be defined.