Journal article
The matricellular protein CCN3 supports lung endothelial homeostasis and function
American journal of physiology. Lung cellular and molecular physiology, Vol.324(2), pp.L154-L168
02/01/2023
DOI: 10.1152/ajplung.00248.2022
PMCID: PMC9925165
PMID: 36573684
Abstract
Aberrant vascular remodeling contributes to the progression of many aging-associated diseases, including idiopathic pulmonary fibrosis (IPF), where heterogeneous capillary density, endothelial transcriptional alterations, and increased vascular permeability correlate with poor disease outcomes. Thus, identifying disease-driving mechanisms in the pulmonary vasculature may be a promising strategy to limit IPF progression. Here, we identified
as an endothelial-derived factor that is upregulated in resolving but not in persistent lung fibrosis in mice, and whose function is critical for vascular homeostasis and repair. Loss and gain of function experiments were carried out to test the role of CCN3 in lung microvascular endothelial function in vitro through RNAi and the addition of recombinant human CCN3 protein, respectively. Endothelial migration, permeability, proliferation, and in vitro angiogenesis were tested in cultured human lung microvascular endothelial cells (ECs). Loss of CCN3 in lung ECs resulted in transcriptional alterations along with impaired wound-healing responses, in vitro angiogenesis, barrier integrity as well as an increased profibrotic activity through paracrine signals, whereas the addition of recombinant CCN3 augmented endothelial function. Altogether, our results demonstrate that the matricellular protein CCN3 plays an important role in lung endothelial function and could serve as a promising therapeutic target to facilitate vascular repair and promote lung fibrosis resolution.
Details
- Title: Subtitle
- The matricellular protein CCN3 supports lung endothelial homeostasis and function
- Creators
- Kalpana R Betageri - Mayo ClinicPatrick A Link - Mayo ClinicAndrew J Haak - Mayo ClinicGiovanni Ligresti - Boston University School of MedicineDaniel J Tschumperlin - Mayo ClinicNunzia Caporarello - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.324(2), pp.L154-L168
- DOI
- 10.1152/ajplung.00248.2022
- PMID
- 36573684
- PMCID
- PMC9925165
- NLM abbreviation
- Am J Physiol Lung Cell Mol Physiol
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Grant note
- R01 HL092961 / NHLBI NIH HHS L30 HL159704 / NHLBI NIH HHS F32 HL158018 / NHLBI NIH HHS R01 HL142596 / NHLBI NIH HHS R01 HL153026 / NHLBI NIH HHS R01 HL158733 / NHLBI NIH HHS T32 HL105355 / NHLBI NIH HHS
- Language
- English
- Date published
- 02/01/2023
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center
- Record Identifier
- 9984948141502771
Metrics
24 Record Views