Molecular pathogenesis of diffuse panbronchiolitis : Evaluation for expression of the airway epithelium-specific genes

弥漫性泛细支气管炎(DPB)是一种主要影响成人的慢性炎症性呼吸道疾病。虽然该病的发病机制尚不清楚，但由于报告的DPB病例主要来自亚洲国家，如日本，因此可能存在遗传易感性。此外，就肺部表现而言，DBP和囊性纤维化(CF)有许多相似之处。首先，为了探讨DPB可能是由呼吸道上皮细胞特异性基因(S)的异常表达所致，我们对DPB患者的基因组DNA和从呼吸道细胞中提取的cc10基因进行了突变分析，到目前为止，尚未发现DPB患者中存在包括DELTAF508在内的主要致病基因突变。此外，在DPB个体中未检测到CC10基因的任何病理性核苷酸替换，这表明DPB的发病机制可能与CC10基因的表达无关。其次，利用从DPB和正常人获得的呼吸道上皮细胞mRNA的差异显示分析显示了几个差异表达的基因。对这些基因的进一步研究目前正在进行中。

Diffuse panbronchiolitis (DPB) is a chronic inflammatory airway disease affecting mainly adults. Although pathogenesis of the disease remains unknown, genetic predisposition is suspected since the reported cases of DPB are predominantly from Asian countries such as Japan. Also, not a few similarities exit between DBP and cystic fibrosis (CF) in terms of pulmonary manifestations. First, to evaluate the possibility that DPB may be caused by abnormal expression of the gene (s) specific to airway epithelium, genomic DNA as well as mRNA extracted from airway cells (after conversion to cDNA) were analyzed for mutations of the CFTR and CC10 genes in individuals with DPB.So far, no disease-causing major CFTR gene mutations including DELTAF508 have been found in DPB individuals. Further, any pathological nucleotide substitution was not detected in the CC10 gene in DPB individuals, suggesting that the pathogenesis of DPB is not likely related to CC10 gene expression. Second, differential display analysis using airway epithelial cell mRNA obtained from DPB and normal individuals revealed several differentially expressed genes. The further investigation on these genes are currently underway.