Secondary alveolar septa are mostly generated after birth in humans and in mice this is completely accomplished postnatally, when mechanical stresses vary as airspace pressure oscillates. Alveolar mesenchymal cells deposit elastic fibers which limit cellular strain, but while the elastic fiber network is incomplete, this function is also served by the intracellular cytoskeleton. Intermediate filament proteins support deformation during cellular division and migration, which occur during septal elongation. Because platelet-derived growth factor-alpha (PDGFRα) signaling is essential for alveolar septation, we hypothesized that neuropilin-1 (NRP1) may link PDGFRα to cytoskeletal deformation. During cell migration, NRP1 links receptor tyrosine kinase signaling to cytoskeletal and focal adhesion remodeling. Therefore, we examined the consequences of nrp1-gene deletion in alveolar mesenchymal cells, including myofibroblasts and pericytes. Neuropilin-1-depletion reduced the proportion of mesenchymal cells which contained nestin and desmin within the sub-population which lacked PDGFRα, but contained PDGFRβ. Desmin was reduced at alveolar entry rings, airspaces were enlarged, and the gas-exchange surface area was reduced after NRP1 depletion. PDGFRα and NRP1 co-localized to membrane lipid rafts, which are known to contain Src-kinase. Neuropilin-1depletion reduced alveolar mesenchymal cell migration and PDGF-A mediated activation of Src-kinase, which may limit the accumulation of desmin at septal tips (alveolar entry rings). Cooperation between Nrp1 and PDGF-signaling is required for secondary septation, and manipulating Nrp1 could promote alveolar regeneration without producing fibrosis.
Pharmacology, Toxicology and Pharmaceutical Science
1
13%
Biochemistry, Genetics and Molecular Biology
1
13%
Nursing and Health Professions
1
13%
Immunology and Microbiology
1
13%
Medicine and Dentistry
1
13%
Other
0
0%
Unknown
3
38%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 March 2018.
All research outputs
#21,946,788
of 34,763,505 outputs
Outputs from American Journal of Physiology: Lung Cellular & Molecular Physiology
#2,921
of 4,000 outputs
Outputs of similar age
#220,538
of 381,543 outputs
Outputs of similar age from American Journal of Physiology: Lung Cellular & Molecular Physiology
#27
of 34 outputs
Altmetric has tracked 34,763,505 research outputs across all sources so far. This one is in the 36th percentile – i.e., 36% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,000 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 381,543 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 34 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.
