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BibTex format

@article{Barratt:2017:10.1164/rccm.201603-0568OC,
author = {Barratt, SL and Blythe, T and Jarrett, C and Ourradi, K and Shelley-Fraser, G and Day, MJ and Qiu, Y and Harper, S and Maher, TM and Oltean, S and Hames, TJ and Scotton, CJ and Welsh, GI and Bates, DO and Millar, AB},
doi = {10.1164/rccm.201603-0568OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {479--493},
title = {Differential Expression of VEGF-Axxx Isoforms Is Critical for Development of Pulmonary Fibrosis.},
url = {http://dx.doi.org/10.1164/rccm.201603-0568OC},
volume = {196},
year = {2017}
}
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TY  - JOUR
AB  - RATIONALE: Fibrosis after lung injury is related to poor outcome, and idiopathic pulmonary fibrosis (IPF) can be regarded as an exemplar. Vascular endothelial growth factor (VEGF)-A has been implicated in this context, but there are conflicting reports as to whether it is a contributory or protective factor. Differential splicing of the VEGF-A gene produces multiple functional isoforms including VEGF-A165a and VEGF-A165b, a member of the inhibitory family. To date there is no clear information on the role of VEGF-A in IPF. OBJECTIVES: To establish VEGF-A isoform expression and functional effects in IPF. METHODS: We used tissue sections, plasma, and lung fibroblasts from patients with IPF and control subjects. In a bleomycin-induced lung fibrosis model we used wild-type MMTV mice and a triple transgenic mouse SPC-rtTA(+/-)TetoCre(+/-)LoxP-VEGF-A(+/+) to conditionally induce VEGF-A isoform deletion specifically in the alveolar type II (ATII) cells of adult mice. MEASUREMENTS AND MAIN RESULTS: IPF and normal lung fibroblasts differentially expressed and responded to VEGF-A165a and VEGF-A165b in terms of proliferation and matrix expression. Increased VEGF-A165b was detected in plasma of progressing patients with IPF. In a mouse model of pulmonary fibrosis, ATII-specific deficiency of VEGF-A or constitutive overexpression of VEGF-A165b inhibited the development of pulmonary fibrosis, as did treatment with intraperitoneal delivery of VEGF-A165b to wild-type mice. CONCLUSIONS: These results indicate that changes in the bioavailability of VEGF-A sourced from ATII cells, namely the ratio of VEGF-Axxxa to VEGF-Axxxb, are critical in development of pulmonary fibrosis and may be a paradigm for the regulation of tissue repair.
AU  - Barratt,SL
AU  - Blythe,T
AU  - Jarrett,C
AU  - Ourradi,K
AU  - Shelley-Fraser,G
AU  - Day,MJ
AU  - Qiu,Y
AU  - Harper,S
AU  - Maher,TM
AU  - Oltean,S
AU  - Hames,TJ
AU  - Scotton,CJ
AU  - Welsh,GI
AU  - Bates,DO
AU  - Millar,AB
DO  - 10.1164/rccm.201603-0568OC
EP  - 493
PY  - 2017///
SN  - 1073-449X
SP  - 479
TI  - Differential Expression of VEGF-Axxx Isoforms Is Critical for Development of Pulmonary Fibrosis.
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.201603-0568OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/28661183
VL  - 196
ER  -
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