Department of Otolaryngology–Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, USA.
Am J Respir Cell Mol Biol. 2011 Aug;45(2):202-20. doi: 10.1165/rcmb.2010-0498TR. Epub 2011 Feb 4.
Cell junction proteins connect epithelial cells to each other and to the basement membrane. Genetic mutations of these proteins can cause alterations in some epithelia leading to varied phenotypes such as deafness, renal disease, skin disorders, and cancer. This review examines if genetic mutations in these proteins affect the function of lung airway epithelia. We review cell junction proteins with examples of disease mutation phenotypes in humans and in mouse knockout models. We also review which of these genes are expressed in airway epithelium by microarray expression profiling and immunocytochemistry. Last, we present a comprehensive literature review to find the lung phenotype when cell junction and adhesion genes are mutated or subject to targeted deletion. We found that in murine models, targeted deletion of cell junction and adhesion genes rarely result in a lung phenotype. Moreover, mutations in these genes in humans have no obvious lung phenotype. Our research suggests that simply because a cell junction or adhesion protein is expressed in an organ does not imply that it will exhibit a drastic phenotype when mutated. One explanation is that because a functioning lung is critical to survival, redundancy in the system is expected. Therefore mutations in a single gene might be compensated by a related function of a similar gene product. Further studies in human and animal models will help us understand the overlap in the function of cell junction gene products. Finally, it is possible that the human lung phenotype is subtle and has not yet been described.
细胞连接蛋白将上皮细胞彼此连接，并与基底膜连接。这些蛋白质的基因突变会导致某些上皮细胞发生改变，从而导致各种表型，如耳聋、肾脏疾病、皮肤疾病和癌症。这篇综述探讨了这些蛋白质的基因突变是否会影响肺气道上皮细胞的功能。我们综述了细胞连接蛋白，并举例说明了人类疾病突变表型和小鼠基因敲除模型中的情况。我们还综述了这些基因在气道上皮细胞中的表达情况，方法是通过微阵列表达谱分析和免疫细胞化学分析。最后，我们进行了全面的文献综述，以寻找细胞连接和黏附基因发生突变或受到靶向删除时的肺部表型。我们发现，在小鼠模型中，细胞连接和黏附基因的靶向删除很少导致肺部表型。此外，人类这些基因的突变没有明显的肺部表型。我们的研究表明，仅仅因为一个细胞连接或黏附蛋白在一个器官中表达，并不意味着当它发生突变时就会表现出明显的表型。一种解释是，由于一个功能正常的肺对生存至关重要，因此系统中存在冗余。因此，单个基因的突变可能会被相关的类似基因产物的功能所补偿。在人类和动物模型中的进一步研究将帮助我们了解细胞连接基因产物功能的重叠。最后，人类肺部表型可能很细微，尚未被描述。
