Chi Yinxiu, Wang Xianhui, Zhang Dongliang, Han Jingjing, Shao Xiaoyun, Xiang Yang, Deng Linhong
Jiangsu Medical College, Yancheng, 224000, Jiangsu, China.
School of Basic Medicine, Central South University, Changsha, 410013, China.
Sci Rep. 2025 Jul 1;15(1):20985. doi: 10.1038/s41598-025-05983-1.
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 ITGB4cells 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.
肺细胞外基质（ECM）的组成和重塑改变对肺发育至关重要。我们的研究发现，条件性敲除整合素β4（Itgb4）的小鼠表现出肺发育异常。在本研究中，我们使用蛋白质免疫印迹和免疫组织化学技术研究了正常小鼠和Itgb4缺陷小鼠中IV型胶原（Col IV）和基质金属蛋白酶9（MMP9）的表达。我们的研究结果表明，Itgb4缺陷导致支气管肺发育不良，其特征是Col IV沉积增加和MMP9表达降低。使用激光共聚焦显微镜评估正常和Col IV包被底物上的紧密连接蛋白1（ZO-1）。同时，通过荧光共振能量转移（FRET）显微镜对RhoA活性进行定量。研究结果表明，ITGB4缺陷细胞中ZO-1显著破坏，同时RhoA活性降低。然而，在Col IV包被底物上的ITGB4细胞中，RhoA活性增强。此外，应用罗辛可增强ITGB4细胞中ZO-1的表达。这些研究结果表明，ITGB4表达降低导致Col IV水平升高，并阻碍支气管上皮细胞的适应性。
