Peri A, Cordella-Miele E, Miele L, Mukherjee A B
Section on Developmental Genetics, Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Invest. 1993 Nov;92(5):2099-109. doi: 10.1172/JCI116810.
Clara cell 10-kD protein (cc10kD), a secretory phospholipase A2 inhibitor, is suggested to be the human counterpart of rabbit uteroglobin (UG). Because cc10kD is expressed constitutively at a very high level in the human respiratory epithelium, the 5' region of its gene may be useful in achieving organ-specific expression of recombinant DNA in gene therapy of diseases such as cystic fibrosis. However, it is important to establish the tissue-specific expression of this gene before designing gene transfer experiments. Since the UG gene in the rabbit is expressed in many other organs besides the lung and the endometrium, we investigated the organ and tissue specificity of human cc10kD gene expression using polymerase chain reaction, nucleotide sequence analysis, immunofluorescence, and Northern blotting. Our results indicate that, in addition to the lung, cc10kD is expressed in several nonrespiratory organs, with a distribution pattern very similar, if not identical, to that of UG in the rabbit. These results underscore the necessity for more detailed analyses of the 5' region of the human cc10kD gene before its usefulness in gene therapy could be fully assessed. These data also suggest that cc10kD and UG may have similar physiological function(s).
克拉拉细胞10-kD蛋白(cc10kD)是一种分泌型磷脂酶A2抑制剂,被认为是兔子宫珠蛋白(UG)的人类对应物。由于cc10kD在人类呼吸道上皮中持续高水平表达,其基因的5'区域可能有助于在诸如囊性纤维化等疾病的基因治疗中实现重组DNA的器官特异性表达。然而,在设计基因转移实验之前,确定该基因的组织特异性表达很重要。由于兔的UG基因除了在肺和子宫内膜中表达外,还在许多其他器官中表达,我们使用聚合酶链反应、核苷酸序列分析、免疫荧光和Northern印迹法研究了人类cc10kD基因表达的器官和组织特异性。我们的结果表明,除了肺之外,cc10kD还在几个非呼吸器官中表达,其分布模式与兔UG的分布模式非常相似(即使不完全相同)。这些结果强调了在充分评估其在基因治疗中的有用性之前,对人类cc10kD基因的5'区域进行更详细分析的必要性。这些数据还表明,cc10kD和UG可能具有相似的生理功能。