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Objectives: To establish VEGF isoform expression and functional effects in IPF.
Methods: We used tissue sections, plasma and lung fibroblasts from IPF patients and controls. 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 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 sera of progressing IPF patients. In a mouse model of pulmonary fibrosis alveolar type II cell (ATII) specific deficiency of VEGF-A or constitutive over-expression of VEGF-A165b inhibited the development of pulmonary fibrosis, as did treatment with intra-peritoneal 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.
|Number of pages||15|
|Journal||American Journal of Respiratory and Critical Care Medicine|
|Early online date||29 Jun 2017|
|Publication status||Published - 15 Aug 2017|
- Vascular Endothelial Growth Factor ( VEGF)
- Pulmonary Fibrosis
- Animal Models of pulmonary fibrosis
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