Cloning of a gene for a novel epithelium-specific cytosolic phospholipase A2, cPLA2δ, induced in psoriatic skin
Cloning of a gene for a novel epithelium-specific cytosolic phospholipase A2, cPLA2δ, induced in psoriatic skin
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DOI：
10.1074/jbc.m305801200
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发表时间：
2004-03-26
影响因子：
4.8
通讯作者：
Imai, Y
中科院分区：
文献类型：
--
作者：
Chiba, H;Michibata, H;Imai, Y
银屑病是一种常见的皮肤病，其特征是增生性再生表皮生长和免疫细胞浸润。银屑病的病因是未知的，虽然几个遗传和细胞因素已被阐明。为了寻找新的银屑病相关基因，我们克隆了正常皮肤和银屑病皮肤之间差异表达的cDNA。在这些克隆中，我们已经确定了一个新的基因，编码IV型胞质磷脂酶A（2）（cPLA（2））家族的一个新成员。我们将该基因称为cPLA（2）delta。它编码818个氨基酸的多肽，在C2和催化结构域中与已知的cPLA（2）蛋白具有显著的同源性。将cPLA（2）δ基因定位于15 q13 - 14染色体基因座，靠近cPLA（2）β基因的基因座，与其相距约220 kb的物理距离。为了鉴定cPLA（2）δ的磷脂酶A（2）活性，我们用His标记的cPLA（2）δ转染COS- 7细胞.这些细胞的裂解液具有钙依赖性磷脂酶A（2）活性.北方印迹分析显示，约4 kb的cPLA（2）δ转录本在复层鳞状上皮中表达，如皮肤和宫颈上皮，但在其他组织中不表达。原位杂交和免疫组织化学显示，cPLA（2）delta在银屑病表皮的上棘层中强烈表达，在特应性皮炎和蕈样霉菌病中弱表达且不连续，在正常皮肤的表皮中未检测到; cPLA（2）alpha在正常皮肤或银屑病皮肤中均未检测到。这些结果表明，与已知的cPLA（2）亚型相比，cPLA（2）delta表现出独特的分布模式，并且它可能在银屑病病变的炎症中起关键作用。
Psoriasis is a common skin disease characterized by hyperplastic regenerative epidermal growth and infiltration of immunocytes. The etiology of psoriasis is unknown, although several genetic and cellular factors have been elucidated. To find new psoriasis- related genes, we have cloned cDNAs that are differentially expressed between normal and psoriatic skins. Among these clones, we have identified a new gene that codes for a new member of the type IV cytosolic phospholipase A(2) ( cPLA(2)) family. We refer to this gene as cPLA(2)delta. It encodes a polypeptide of 818 amino acids that has significant homology with known cPLA(2) proteins in the C2 and catalytic domains. The cPLA(2)delta gene was mapped to the 15q13 - 14 chromosomal locus, near to the locus of the cPLA(2)beta gene, from which it is separated by a physical distance of about 220 kb. To identify the phospholipase A(2) activity of cPLA(2)delta, we transfected COS- 7 cells with His- tagged cPLA(2)delta. The cell lysate from these cells had calcium- dependent phospholipase A(2) activity. Northern blot analysis revealed that a cPLA(2)delta transcript of about 4 kb is expressed in stratified squamous epithelia, such as those in skin and cervix, but not in other tissues. In situ hybridization and immunohistochemistry revealed that cPLA(2)delta is expressed strongly in the upper spinous layer of the psoriatic epidermis, expressed weakly and discontinuously in atopic dermatitis and mycosis fungoides, and not detected in the epidermis of normal skin; cPLA(2)alpha is not detected in either normal or psoriatic skin. These results suggest that cPLA(2)delta exhibits a unique distribution pattern compared with that of known cPLA(2) subtypes, and it may play a critical role in inflammation in psoriatic lesions.