Endothelial progenitor cells stimulate neonatal lung angiogenesis through FOXF1-mediated activation of BMP9/ACVRL1 signaling

Guolun Wang, Bingqiang Wen, Zicheng Deng, Yufang Zhang, Olena A. Kolesnichenko, Vladimir Ustiyan, Arun Pradhan, Tanya V. Kalin and Vladimir V. Kalinichenko ()
Additional contact information
Guolun Wang: Center for Lung Regenerative Medicine, Perinatal Institute, Cincinnati Children’s Hospital Medical Center
Bingqiang Wen: Center for Lung Regenerative Medicine, Perinatal Institute, Cincinnati Children’s Hospital Medical Center
Zicheng Deng: Center for Lung Regenerative Medicine, Perinatal Institute, Cincinnati Children’s Hospital Medical Center
Yufang Zhang: Center for Lung Regenerative Medicine, Perinatal Institute, Cincinnati Children’s Hospital Medical Center
Olena A. Kolesnichenko: Center for Lung Regenerative Medicine, Perinatal Institute, Cincinnati Children’s Hospital Medical Center
Vladimir Ustiyan: Center for Lung Regenerative Medicine, Perinatal Institute, Cincinnati Children’s Hospital Medical Center
Arun Pradhan: Center for Lung Regenerative Medicine, Perinatal Institute, Cincinnati Children’s Hospital Medical Center
Tanya V. Kalin: Cincinnati Children’s Hospital Medical Center
Vladimir V. Kalinichenko: Center for Lung Regenerative Medicine, Perinatal Institute, Cincinnati Children’s Hospital Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Pulmonary endothelial progenitor cells (EPCs) are critical for neonatal lung angiogenesis and represent a subset of general capillary cells (gCAPs). Molecular mechanisms through which EPCs stimulate lung angiogenesis are unknown. Herein, we used single-cell RNA sequencing to identify the BMP9/ACVRL1/SMAD1 pathway signature in pulmonary EPCs. BMP9 receptor, ACVRL1, and its downstream target genes were inhibited in EPCs from Foxf1WT/S52F mutant mice, a model of alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). Expression of ACVRL1 and its targets were reduced in lungs of ACDMPV subjects. Inhibition of FOXF1 transcription factor reduced BMP9/ACVRL1 signaling and decreased angiogenesis in vitro. FOXF1 synergized with ETS transcription factor FLI1 to activate ACVRL1 promoter. Nanoparticle-mediated silencing of ACVRL1 in newborn mice decreased neonatal lung angiogenesis and alveolarization. Treatment with BMP9 restored lung angiogenesis and alveolarization in ACVRL1-deficient and Foxf1WT/S52F mice. Altogether, EPCs promote neonatal lung angiogenesis and alveolarization through FOXF1-mediated activation of BMP9/ACVRL1 signaling.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-29746-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29746-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-29746-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().