Deficiency of integrin β4 contributes bronchopulmonary dysplasia by compromising cellular stability through the activation of RhoA-(ZO-1) signaling pathways.

Alterations in the composition and remodeling of the lung extracellular matrix (ECM) are critical for lung development. Our research identified that mice with a conditional knockout of integrin β4 (Itgb4) exhibit lung dysplasia. In this study, we investigated the expression of collagen IV (Col IV) and matrix metalloproteinase 9 (MMP9) in both normal and Itgb4-deficient mice using Western blot and immunohistochemistry techniques. Our findings indicate that Itgb4 deficiency results in bronchopulmonary dysplasia, which is characterized by increased deposition of Col IV and reduced expression of MMP9. The zonula occludens-1 (ZO-1), on both normal and Col IV-coated substrates was assessed using laser confocal microscopy. Concurrently, RhoA activities were quantified via fluorescence resonance energy transfer (FRET) microscopy. The findings indicated a significant disruption of ZO-1 in ITGB4-deficient cells, accompanied by an dcrease in RhoA activity.However, RhoA activity was enhanced in ITGB4(-/-)cells on the Col IV-coated substrate. Furthermore, the application of rhosin resulted in an enhanced expression of ZO-1 in ITGB4(-/-) cells. These findings indicate that reduced expression of ITGB4 leads to elevated levels of Col IV and hinders the adaptation of bronchial epithelial cells.