Lung-specific loss of the laminin α3 subunit confers resistance to mechanical injury.

Abstract:

: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 α3 laminin (Lama3(fl/fl)), one of the main laminin subunits in the lung basement membrane. At 60 days after intratracheal treatment of adult Lama3(fl/fl) mice with an adenovirus encoding Cre recombinase (Ad-Cre), the protein abundance of α3 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 α3 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 α3 laminin subunit resulted in evidence of lung inflammation. However, this did not account for their resistance to mechanical ventilation. Rather, the loss of α3 laminin was associated with a significant increase in the collagen content of the lungs. We conclude that the loss of α3 laminin in the alveolar epithelium results in an increase in lung collagen, which confers resistance to mechanical injury.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Urich D,Eisenberg JL,Hamill KJ,Takawira D,Chiarella SE,Soberanes S,Gonzalez A,Koentgen F,Manghi T,Hopkinson SB,Misharin AV,Perlman H,Mutlu GM,Budinger GR,Jones JC

doi

10.1242/jcs.080911

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

2927-37

issue

Pt 17

eissn

0021-9533

issn

1477-9137

pii

124/17/2927

journal_volume

124

pub_type

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