Microsatellite instability in transforming growth factor-beta 1 type II receptor gene in alveolar lining epithelial cells of idiopathic pulmonary fibrosis

It has been reported that transforming growth factor (TC F)-beta, which pla ys an integral role in the pathogenesis of idiopathic pulmonary fibrosis (I PF), suppresses proliferation of alveolar epithelial cells in vitro. Althou gh hyperplastic lesions of alveolar lining epithelial cells (ALECs) are cha racteristic pathologic features of IPF, the mechanism of their involvement in the pathogenesis has not yet been extensively studied. On the assumption that the hyperplastic ALECs have escaped from the growth-inhibitory effect s of TCF-beta, we searched for mutations in the microsatellite of the TCF-b eta receptor type II (T beta RII) gene. To detect a deletion in the polyade nine tract in exon 3 of the T beta RII gene, cells were isolated by microdi ssection from lung sections of IPF patients, and DNA was extracted from the se cells and amplified by high-fidelity polymerase chain reaction. A total of 121 sites of hyperplastic ALECs from 11 IPF patients were analyzed, and a one-base-pair deletion was detected in nine sites from five patients. The mutation was also detected in smooth muscle-like cells of the thickened pu lmonary artery. In some tissue areas where the deletion was detected, low T beta RII expression was confirmed by immunohistochemical staining. These d ata suggest that microsatellite instability in the T beta RII gene occurred in some lesions of hyperplastic ALECs in IPF, although at a low incidence, and that this genetic disorder might play a partial role in the pathologic changes of IPF.