Journal article
Dichotomous role of integrin-beta 5 in lung endothelial cells
Pulmonary circulation, Vol.12(4), 12156
10/01/2022
DOI: 10.1002/pul2.12156
PMCID: PMC9684688
PMID: 36438452
Abstract
Pulmonary arterial hypertension (PAH) is a progressive, devastating disease, and its main histological manifestation is an occlusive pulmonary arteriopathy. One important functional component of PAH is aberrant endothelial cell (EC) function including apoptosis-resistance, unchecked proliferation, and impaired migration. The mechanisms leading to and maintaining physiologic and aberrant EC function are not fully understood. Here, we tested the hypothesis that in PAH, ECs have increased expression of the transmembrane protein integrin-beta 5, which contributes to migration and survival under physiologic and pathological conditions, but also to endothelial-to-mesenchymal transition (EnMT). We found that elevated integrin-beta 5 expression in pulmonary artery lesions and lung tissue from PAH patients and rats with PH induced by chronic hypoxia and injection of CD117(+) rat lung EC clones. These EC clones exhibited elevated expression of integrin-beta 5 and its heterodimerization partner integrin-alpha nu and showed accelerated barrier formation. Inhibition of integrin-alpha nu beta 5 in vitro partially blocked transforming growth factor (TGF)-beta 1-induced EnMT gene expression in rat lung control ECs and less in rat lung EC clones and human lung microvascular ECs. Inhibition of integrin-alpha nu beta 5 promoted endothelial dysfunction as shown by reduced migration in a scratch assay and increased apoptosis in synergism with TGF-beta 1. In vivo, blocking of integrin-alpha nu beta 5 exaggerated PH induced by chronic hypoxia and CD117(+) EC clones in rats. In summary, we found a role for integrin-alpha nu beta 5 in lung endothelial survival and migration, but also a partial contribution to TGF-beta 1-induced EnMT gene expression. Our results suggest that integrin-alpha nu beta 5 is required for physiologic function of ECs and lung vascular homeostasis.
Details
- Title: Subtitle
- Dichotomous role of integrin-beta 5 in lung endothelial cells
- Creators
- Neil Blanchard - University of VirginiaPatrick A. Link - Mayo Clinic in FloridaDaniela Farkas - The Ohio State University Wexner Medical CenterBrennan Harmon - Children's NationalJaylen Hudson - The Ohio State University Wexner Medical CenterSrimathi Bogamuwa - The Ohio State University Wexner Medical CenterBryce Piper - The Ohio State University Wexner Medical CenterKayla Authelet - Children's NationalCarlyne D. Cool - University of Colorado DenverRebecca L. Heise - Virginia Commonwealth UniversityRobert Freishtat - Children's NationalLaszlo Farkas - The Ohio State University Wexner Medical Center
- Resource Type
- Journal article
- Publication Details
- Pulmonary circulation, Vol.12(4), 12156
- DOI
- 10.1002/pul2.12156
- PMID
- 36438452
- PMCID
- PMC9684688
- NLM abbreviation
- Pulm Circ
- ISSN
- 2045-8932
- eISSN
- 2045-8940
- Publisher
- Wiley
- Number of pages
- 16
- Grant note
- CA016059; HL123044; HL139881 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 10/01/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center
- Record Identifier
- 9984948044002771
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