Golpon H A, Geraci M W, Moore M D, Miller H L, Miller G J, Tuder R M, Voelkel N F
Pulmonary Hypertension Center, University of Colorado Health Sciences Center, 4200 E. Ninth Ave., Denver, CO 80262, USA.
Am J Pathol. 2001 Mar;158(3):955-66. doi: 10.1016/S0002-9440(10)64042-4.
HOX genes belong to the large family of homeodomain genes that function as transcription factors. Animal studies indicate that they play an essential role in lung development. We investigated the expression pattern of HOX genes in human lung tissue by using microarray and degenerate reverse transcriptase-polymerase chain reaction survey techniques. HOX genes predominantly from the 3' end of clusters A and B were expressed in normal human adult lung and among them HOXA5 was the most abundant, followed by HOXB2 and HOXB6. In fetal (12 weeks old) and diseased lung specimens (emphysema, primary pulmonary hypertension) additional HOX genes from clusters C and D were expressed. Using in situ hybridization, transcripts for HOXA5 were predominantly found in alveolar septal and epithelial cells, both in normal and diseased lungs. A 2.5-fold increase in HOXA5 mRNA expression was demonstrated by quantitative reverse transcriptase-polymerase chain reaction in primary pulmonary hypertension lung specimens when compared to normal lung tissue. In conclusion, we demonstrate that HOX genes are selectively expressed in the human lung. Differences in the pattern of HOX gene expression exist among fetal, adult, and diseased lung specimens. The altered pattern of HOX gene expression may contribute to the development of pulmonary diseases.
HOX基因属于作为转录因子发挥作用的同源结构域基因大家族。动物研究表明，它们在肺发育中起重要作用。我们通过使用微阵列和简并逆转录聚合酶链反应检测技术，研究了HOX基因在人肺组织中的表达模式。主要来自A簇和B簇3'端的HOX基因在正常成人肺中表达，其中HOXA5表达量最高，其次是HOXB2和HOXB6。在胎儿（12周龄）和患病肺标本（肺气肿、原发性肺动脉高压）中，C簇和D簇的其他HOX基因也有表达。使用原位杂交技术，在正常和患病肺中，HOXA5的转录本主要存在于肺泡间隔和上皮细胞中。与正常肺组织相比，原发性肺动脉高压肺标本中HOXA5 mRNA表达通过定量逆转录聚合酶链反应显示增加了2.5倍。总之，我们证明HOX基因在人肺中选择性表达。胎儿、成人和患病肺标本中HOX基因表达模式存在差异。HOX基因表达模式的改变可能有助于肺部疾病的发展。
