Microsatellite Instability in Transforming Growth Factor - Betal Type II Receptor Gene in Alveolar Lining Epithelial Cells of Idiopathic Pulmonary Fibrosis

据报道，转化生长因子(TGF)-β在特发性肺纤维化（IPF）的发病机制中起着不可或缺的作用。假设增生性肺泡衬上皮细胞（ALECs）是IPF的典型病理特征，已经摆脱了TGF-β的生长抑制作用，我们寻找TGF-β受体II型（t -β rii）基因微卫星的突变。为了检测TβRII基因外显子3多腺嘌呤束的缺失，我们从IPF患者的肺切片上通过显微解剖分离细胞，提取细胞DNA并进行高保真PCR扩增。对11例IPF患者的增生性ALECs的121个位点进行分析，在5例患者的9个位点检测到1个碱基对缺失。在增厚的肺动脉平滑肌样细胞中也检测到这种突变。在一些缺失的组织区域，免疫组织化学染色证实TβRII低表达。在非特异性间质性肺炎（NSIP）中，我们也在2例NSIP中检测到1例TβRII基因缺失。这些数据表明，TβRII基因微卫星不稳定性在IPF增生性ALECs的一些病变中发生，尽管发生率较低，这种遗传疾病可能在包括IPF在内的肺纤维化病理改变中起部分作用。

It has been reported that transforming growth factor (TGF)-β, which plays an integral role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). On the assumption that the hyperplastic alveolar lining epithelial cells (ALECs) which are characteristic pathologic features of IPF, have escaped from the growth inhibitory effects of TGF-β, we searched for mutations in the microsatellite of the TGF-β receptor type II (TβRII) gene. To detect a deletion in the polyadenine tract in exon 3 of the TβRII gene, cells were isolated by microdissection from lung sections of IPF patients, and DNA was extracted from these cells and amplified by high fidelity PCR.A total of 121 sites of hyperplastic ALECs from 11 IPF patients were analyzed, and a one-base-pair deletion was detected in 9 sites from 5 patients. The mutation was also detected in smooth muscle-like cells of the thickened pulmonary artery. In some tissue areas where the deletion was detected, low TβRII expression was confirmed by immunohistochemical staining. In non-specific interstitial pneumonia (NSIP), we also detected the deletion in the TβRII gene in one case of NSIP out of two. These data suggest that microsatellite instability in the TβRII gene occurred in some lesions of hyperplastic ALECs in IPF, although at a low incidence, and this genetic disorder might play a partial role in the pathologic changes of pulmonary fibrosis including IPF.