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Type IV collagen drives alveolar epithelial–endothelial association and the morphogenetic movements of septation

Overview of attention for article published in BMC Biology, July 2016
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Title
Type IV collagen drives alveolar epithelial–endothelial association and the morphogenetic movements of septation
Published in
BMC Biology, July 2016
DOI 10.1186/s12915-016-0281-2
Pubmed ID
Authors

Maria Loscertales, Fotini Nicolaou, Marion Jeanne, Mauro Longoni, Douglas B. Gould, Yunwei Sun, Faouzi I. Maalouf, Nandor Nagy, Patricia K. Donahoe

Abstract

Type IV collagen is the main component of the basement membrane that gives strength to the blood-gas barrier (BGB). In mammals, the formation of a mature BGB occurs primarily after birth during alveologenesis and requires the formation of septa from the walls of the saccule. In contrast, in avians, the formation of the BGB occurs rapidly and prior to hatching. Mutation in basement membrane components results in an abnormal alveolar phenotype; however, the specific role of type IV collagen in regulating alveologenesis remains unknown. We have performed a microarray expression analysis in late chick lung development and found that COL4A1 and COL4A2 were among the most significantly upregulated genes during the formation of the avian BGB. Using mouse models, we discovered that mutations in murine Col4a1 and Col4a2 genes affected the balance between lung epithelial progenitors and differentiated cells. Mutations in Col4a1 derived from the vascular component were sufficient to cause defects in vascular development and the BGB. We also show that Col4a1 and Col4a2 mutants displayed disrupted myofibroblast proliferation, differentiation and migration. Lastly, we revealed that addition of type IV collagen protein induced myofibroblast proliferation and migration in monolayer culture and increased the formation of mesenchymal-epithelial septal-like structures in co-culture. Our study showed that type IV collagen and, therefore the basement membrane, play fundamental roles in coordinating alveolar morphogenesis. In addition to its role in the formation of epithelium and vasculature, type IV collagen appears to be key for alveolar myofibroblast development by inducing their proliferation, differentiation and migration throughout the developing septum.

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Mendeley readers

The data shown below were compiled from readership statistics for 72 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 1%
Unknown 71 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 21%
Researcher 10 14%
Student > Bachelor 7 10%
Student > Doctoral Student 5 7%
Student > Master 5 7%
Other 9 13%
Unknown 21 29%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 15%
Medicine and Dentistry 10 14%
Agricultural and Biological Sciences 10 14%
Engineering 5 7%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Other 8 11%
Unknown 25 35%