Disruption of plasminogen activator inhibitor-1 gene enhances spontaneous enlargement of mouse airspace with increasing age

5Citations
Citations of this article
7Readers
Mendeley users who have this article in their library.

Abstract

Plasminogen activator inhibitor-1 (PAI-1) is the most effective protease inhibitor in the fibrinolysis system, and plays an important role in the remodeling of the extracellular matrix. We therefore explored whether PAI-1 is involved in the change of lung structure with increasing age. PAI-1 gene knockout mice and wild-type mice were sacrificed at age 3 weeks, 3 months, 6 months and 15 months for histopathology analysis, and assessed the relationship between PAI-1 and the change in lung structure with age. Six-month-old mice were chosen for further studies. Elastin in the lung was detected using Weigert staining. We measured the expression of matrix metalloproteinase-12 (MMP-12) that is a major protease in elastin degradation by real time PCR and immunostaining. Transforming growth factor-β1 (TGF-β1) expression was measured by western blot analysis. PAI-1 gene knockout mice showed significant increases in alveolar size with increasing age and damaged alveolar structure at the age of 15 months, compared with wild-type mice. At the age of 6 months, elastin protein was decreased in the lungs of PAI-1 gene knockout mice. PAI-1 null mice had higher MMP-12 mRNA expression, and lower expression level of active TGF-β1 in the lung. Taken together, these results indicate that the emphysema-like change attributed to PAI-1 deficiency might be facilitated with increased MMP-12 expression that accelerates elastin degradation in mice lungs, and TGF-β1 might be involved in the modulation of this process. © 2010 Tohoku University Medical Press.

Cite

CITATION STYLE

APA

Hu, H., Zhao, Y., Xiao, Y., Zhang, R., & Song, H. (2010). Disruption of plasminogen activator inhibitor-1 gene enhances spontaneous enlargement of mouse airspace with increasing age. Tohoku Journal of Experimental Medicine, 222(4), 291–296. https://doi.org/10.1620/tjem.222.291

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free