RGD Reference Report - Pulmonary vascular permeability and ischemic injury in gelsolin-deficient mice. - Rat Genome Database

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Pulmonary vascular permeability and ischemic injury in gelsolin-deficient mice.

Authors: Becker, Patrice M  Kazi, Armina A  Wadgaonkar, Raj  Pearse, David B  Kwiatkowski, David  Garcia, Joe G N 
Citation: Becker PM, etal., Am J Respir Cell Mol Biol. 2003 Apr;28(4):478-84. doi: 10.1165/rcmb.2002-0024OC.
RGD ID: 329333024
Pubmed: PMID:12654637   (View Abstract at PubMed)
DOI: DOI:10.1165/rcmb.2002-0024OC   (Journal Full-text)

Gelsolin is a potent actin filament regulatory protein that controls cytoskeletal assembly and disassembly. Because cellular gelsolin deficiency leads to pronounced actin stress fiber formation and defective chemotaxis, and similar cytoskeletal remodeling results in endothelial barrier dysfunction, we hypothesized that gelsolin deficient mice would exhibit increased vascular permeability. To test this hypothesis, we compared baseline lung lavage (BAL) protein concentration, wet/dry weight ratio, and osmotic reflection coefficient for albumin (sigma alb) in gelsolin-deficient (gsn-/-) and C57BL/6 (wild-type) mice. In addition, we assessed lung permeability in response to ischemia by evaluating BAL protein concentration after 4, 8, or 24 h of left pulmonary arterial (LPA) occlusion, and lung wet/dry weight ratio and histology after 24 h of LPA occlusion, in gsn-/- and wild-type animals, as compared with control and sham-operated mice. Baseline measurements revealed that BAL protein concentration was 18-fold higher in gsn-/- than in wild-type mice, whereas sigma alb averaged 0.62 + 0.15 in wild-type, as compared with 0.31 + 0.05 in gsn-/- animals, indicating that gelsolin deficiency caused increased pulmonary vascular permeability. Ischemia increased lung permeability (BAL protein and lung wet/dry weight) in both wild-type and gsn-/- mice. However, whereas the fold-increase in BAL protein concentration was less in gsn-/- mice (2- to 4-fold) as compared with wild-type (22- to 34-fold), the duration of ischemia-induced permeability changes was prolonged. Lung wet/dry weight and gross histology following ischemia were comparable in wild-type and gsn-/- animals. These data suggest that gelsolin significantly contributes to maintenance of vascular barrier function in the lung.




  
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Original Reference(s)
GSNHumanpulmonary artery disease severityISOGsn (Mus musculus)associated with ischemiaRGD 
GsnRatpulmonary artery disease severityISOGsn (Mus musculus)associated with ischemiaRGD 
GsnMousepulmonary artery disease severityIMP associated with ischemiaRGD 


Genes (Rattus norvegicus)
Gsn  (gelsolin)

Genes (Mus musculus)
Gsn  (gelsolin)

Genes (Homo sapiens)
GSN  (gelsolin)