Journal
JOURNAL OF CELL SCIENCE
Volume 124, Issue 17, Pages 2927-2937Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.080911
Keywords
Laminin; Extracellular matrix; Lung; Basement membrane
Categories
Funding
- NIH [HL092963, ES015024, ES013995, HL071643, AR050250, AR054796, AR055503, AI067590]
- American Lung Association
- Northwestern University Clinical and Translational Sciences Institute (NUCATS) [UL1 RR025741]
- Northwestern University, Feinberg School of Medicine
Ask authors/readers for more resources
Laminins are heterotrimeric glycoproteins of the extracellular matrix that are secreted by epithelial cells and which are crucial for the normal structure and function of the basement membrane. We have generated a mouse harboring a conditional knockout of alpha 3 laminin (Lama3fl/fl), one of the main laminin subunits in the lung basement membrane. At 60 days after intratracheal treatment of adult Lama3fl/fl mice with an adenovirus encoding Cre recombinase (Ad-Cre), the protein abundance of alpha 3 laminin in whole lung homogenates was more than 50% lower than that in control-treated mice, suggesting a relatively long half-life for the protein in the lung. Upon exposure to an injurious ventilation strategy (tidal volume of 35 ml per kg of body weight for 2 hours), the mice with a knockdown of the alpha 3 laminin subunit had less severe injury, as shown by lung mechanics, histology, alveolar capillary permeability and survival when compared with Ad-Null-treated mice. Knockdown of the alpha 3 laminin subunit resulted in evidence of lung inflammation. However, this did not account for their resistance to mechanical ventilation. Rather, the loss of alpha 3 laminin was associated with a significant increase in the collagen content of the lungs. We conclude that the loss of alpha 3 laminin in the alveolar epithelium results in an increase in lung collagen, which confers resistance to mechanical injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available