EXPLORING THE DUAL ROLE OF VEGF165 IN BLEOMYCIN INDUCED LUNG INJURY AND RECOVERY IN A AAV MICE MODEL
ORCID
https://orcid.org/0009-0007-0407-4989
Date of Award
2024
Document Type
Dissertation
Degree Name
Philosophy (Ph.D)
Department
Pharmaceutical Sciences
First Advisor
Ashley Martino
Second Advisor
Joseph Cerreta
Third Advisor
Sandra Reznik
Abstract
Pulmonary fibrosis (PF) poses a significant challenge in respiratory medicine due to its complex etiology and progression characterized by excessive lung scarring, leading to compromised pulmonary function. The multifaceted roles of Vascular Endothelial Growth Factor A (VEGF-A) and specifically its isoform VEGF-A165 are critical in this context, given their involvement in angiogenesis, lymphangiogenesis, and tissue repair. The dual nature of VEGF-A165, promoting angiogenesis and potentially exacerbating or mitigating fibrosis, underscores its significance in both the progression and recovery phases of PF. Our work, explores the nuanced functions of VEGF-A165 using AAV1 as a gene delivery vector to overexpress this growth factor in lung tissues, thus providing a stable, specific, and safe method for studying the long-term effects on pulmonary fibrosis progression and recovery. The study underscores the potential of VEGF-A165 modulation as a therapeutic target for PF, creates a potential for injury mitigation and enhanced tissue repair. We examined the multifaceted impact of VEGF-A165 on pulmonary fibrosis, using both in vitro and in vivo approaches in an established bleomycin-induced mouse fibrosis model. Our results indicate that VEGF-A165 overexpression, while promoting cell migration and tissue repair, paradoxically exacerbates bleomycin-induced cytotoxicity in vitro, suggesting a delicate balance in its physiological role that is time dependent. In vivo, overexpression of VEGF-A165 increased inflammatory responses and fibrotic scarring, whereas its inhibition with SU5416 reduced cytokine levels, fibrosis, and preserved alveolar architecture. These contradictory roles of VEGF-A165 underscore the complexity of its function in lung injury and highlight the necessity for precise modulation in therapeutic strategies for chronic lung diseases. The study's comprehensive analysis points towards a potential dual role of VEGF-A165 in lung disease, offering a promising avenue for targeted therapy development in COPD and fibrosis.
Recommended Citation
Ban, Igor, "EXPLORING THE DUAL ROLE OF VEGF165 IN BLEOMYCIN INDUCED LUNG INJURY AND RECOVERY IN A AAV MICE MODEL" (2024). Theses and Dissertations. 814.
https://scholar.stjohns.edu/theses_dissertations/814