Imperial College London
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DrMatthewHind

Faculty of Medicine, National Heart & Lung Institute

Honorary Research Officer
 
 
 
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m.hind

 
 
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Location

 

Royal BromptonRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Poobalasingam:2017:10.1242/dmm.028175,
author = {Poobalasingam, T and Yates, LL and Walker, SA and Pereira, M and Gross, NY and Ali, A and Kolatsi-Joannou, M and Jarvelin, MR and Pekkanen, J and Papakrivopoulou, E and Long, DA and Griffiths, M and Wagner, D and Konigshoff, M and Hind, M and Minelli, C and Lloyd, CM and Dean, C},
doi = {10.1242/dmm.028175},
journal = {Disease Models & Mechanisms},
pages = {409--423},
title = {Heterozygous Vangl2 looptail mice reveal novel roles for the planar cell polarity pathway in adult lung homeostasis and repair},
url = {http://dx.doi.org/10.1242/dmm.028175},
volume = {10},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Lung diseases impose a huge economic and health burden worldwide. A key aspect of several adult lung diseases, such as Idiopathic pulmonary fibrosis (IPF) and Chronic Obstructive pulmonary Disease (COPD), including emphysema, is aberrant tissue repair, which leads to an accumulation of damage and impaired respiratory function. Currently, there are few effective treatments available for these diseases and their incidence is rising.The Planar Cell Polarity (PCP) pathway is critical for the embryonic development of many organs, including kidney and lung. We have previously shown that perturbation of the PCP pathway impairs tissue morphogenesis, which disrupts the number and shape of epithelial tubes formed within these organs during embryogenesis. However, very little is known about the role of the PCP pathway beyond birth, partly due to the perinatal lethality of many PCP mouse mutant lines.Here we have investigated heterozygous Looptail (Lp) mice, in which a single copy of the core PCP gene, Vangl2, is disrupted. We show that these mice are viable but display severe airspace enlargement and impaired adult lung function. Underlying these defects, we find that Vangl2Lp/+ lungs exhibit altered distribution of actin microfilaments and abnormal regulation of the actin modifying protein cofilin. In addition, we show that Vangl2Lp/+ lungs exhibit many of the hallmarks of tissue damage including an altered macrophage population, abnormal elastin deposition and elevated levels of the elastin-modifying enzyme, Mmp12, all of which are observed in the lung disease, emphysema.In vitro, VANGL2 disruption impairs directed cell migration and reduces the rate of repair following scratch wounding of human alveolar epithelial cells. Moreover, using population data from a birth cohort of young adults, all aged 31, we found evidence of an interactive effect between VANGL2 and smoking (a tissue damaging insult) on lung function. Finally, we show that that PCP genes VANGL2 and SCRIBBLE (SC
AU  - Poobalasingam,T
AU  - Yates,LL
AU  - Walker,SA
AU  - Pereira,M
AU  - Gross,NY
AU  - Ali,A
AU  - Kolatsi-Joannou,M
AU  - Jarvelin,MR
AU  - Pekkanen,J
AU  - Papakrivopoulou,E
AU  - Long,DA
AU  - Griffiths,M
AU  - Wagner,D
AU  - Konigshoff,M
AU  - Hind,M
AU  - Minelli,C
AU  - Lloyd,CM
AU  - Dean,C
DO  - 10.1242/dmm.028175
EP  - 423
PY  - 2017///
SN  - 1754-8403
SP  - 409
TI  - Heterozygous Vangl2 looptail mice reveal novel roles for the planar cell polarity pathway in adult lung homeostasis and repair
T2  - Disease Models & Mechanisms
UR  - http://dx.doi.org/10.1242/dmm.028175
UR  - http://hdl.handle.net/10044/1/44784
VL  - 10
ER  -
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