التفاصيل البيبلوغرافية
| العنوان: |
Heterozygous Vangl2Looptail mice reveal novel roles for the planar cell polarity pathway in adult lung homeostasis and repair |
| المؤلفون: |
Poobalasingam, T. (Thanushiyan), Yates, L. L. (Laura L.), Walker, S. A. (Simone A.), Pereira, M. (Miguel), Gross, N. Y. (Nina Y.), Ali, A. (Akmol), Kolatsi-Joannou, M. (Maria), Järvelin, M.-R. (Marjo-Riitta), Pekkanen, J. (Juha), Papakrivopoulou, E. (Eugenia), Long, D. A. (David A.), Griffiths, M. (Mark), Wagner, D. (Darcy), Königshoff, M. (Melanie), Hind, M. (Matthew), Minelli, C. (Cosetta), Lloyd, C. M. (Clare M.), Dean, C. H. (Charlotte H.) |
| بيانات النشر: |
Company of Biologists |
| سنة النشر: |
2017 |
| المجموعة: |
Jultika - University of Oulu repository / Oulun yliopiston julkaisuarkisto |
| مصطلحات موضوعية: |
Lung disease, Lung homeostasis, Planar cell polarity, Tissue repair, Vangl2, cytoskeleton |
| الوصف: |
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 because of the perinatal lethality of many PCP mouse mutant lines. Here, we investigate 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 emphysema. In vitro, disruption of VANGL2 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 on lung function. Finally, we show that PCP genes VANGL2 and SCRIB are significantly downregulated in lung tissue from patients with emphysema. Our data ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
info:eu-repo/semantics/altIdentifier/pissn/1754-8403; info:eu-repo/semantics/altIdentifier/eissn/1754-8411 |
| الإتاحة: |
http://urn.fi/urn:nbn:fi-fe201705296938Test |
| حقوق: |
info:eu-repo/semantics/openAccess ; © 2017. The authors. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0Test), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. ; https://creativecommons.org/licenses/by/3.0Test/ |
| رقم الانضمام: |
edsbas.92F82467 |
| قاعدة البيانات: |
BASE |
