Murine insulin growth factor-like (IGFL) and human IGFL1 proteins are induced in inflammatory skin conditions and bind to a novel tumor necrosis factor receptor family member, IGFLR1.
Murine insulin growth factor-like (IGFL) and human IGFL1 proteins are induced in inflammatory skin conditions and bind to a novel tumor necrosis factor receptor family member, IGFLR1.
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在炎症性皮肤条件下诱导鼠类胰岛素生长因子样（IGFL）和人IGFL1蛋白，并与新型肿瘤坏死因子受体家族成员IGFLR1结合。
DOI：
10.1074/jbc.m111.224626
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发表时间：
2011-05-27
期刊：
影响因子：
--
通讯作者：
Gonzalez LC
中科院分区：
文献类型：
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作者：
Lobito AA;Ramani SR;Tom I;Bazan JF;Luis E;Fairbrother WJ;Ouyang W;Gonzalez LC
银屑病是一种以表皮过度增殖和多种白细胞群渗透为特征的人类皮肤疾病。在鉴定一种新的小鼠胰岛素生长因子(IGF)样(IGFL)基因(MIGFL)时，我们发现该基因的转录本在皮肤中表达最高，在皮肤损伤和银屑病样炎症模型中表达增强。一种可能的人类功能同源基因IGFL1在牛皮癣皮肤样本中被独特而显著地诱导。体外培养的原代角质形成细胞在肿瘤坏死因子α刺激下表达上调，但不受其他银屑病相关细胞因子的刺激。最后，利用分泌和跨膜蛋白文库，我们发现了人IGFL1和mIGFL之间以及TMEM149胞外区之间的高亲和力相互作用。TMEM149(这里改名为IGFL1)是一个结构上与肿瘤坏死因子受体家族相似的未知基因。我们的研究表明IGFl1主要在小鼠T细胞表面表达。MIGFL和IGFl1受体之间的联系提示mIGFL可能影响炎症性皮肤条件下的T细胞生物学。
Psoriasis is a human skin condition characterized by epidermal hyperproliferation and infiltration of multiple leukocyte populations. In characterizing a novel insulin growth factor (IGF)-like (IGFL) gene in mice (mIGFL), we found transcripts of this gene to be most highly expressed in skin with enhanced expression in models of skin wounding and psoriatic-like inflammation. A possible functional ortholog in humans, IGFL1, was uniquely and significantly induced in psoriatic skin samples. In vitro IGFL1 expression was up-regulated in cultured primary keratinocytes stimulated with tumor necrosis factor α but not by other psoriasis-associated cytokines. Finally, using a secreted and transmembrane protein library, we discovered high affinity interactions between human IGFL1 and mIGFL and the TMEM149 ectodomain. TMEM149 (renamed here as IGFLR1) is an uncharacterized gene with structural similarity to the tumor necrosis factor receptor family. Our studies demonstrate that IGFLR1 is expressed primarily on the surface of mouse T cells. The connection between mIGFL and IGFLR1 receptor suggests mIGFL may influence T cell biology within inflammatory skin conditions.