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Palit, S.* ; Shrestha, A.K.* ; Thapa, S.* ; L Grimm, S.* ; Coarfa, C.* ; Theis, F.J. ; Simon, L.M.* ; Shivanna, B.*

Leveraging integrated RNA sequencing to decipher adrenomedullin's protective mechanisms in experimental bronchopulmonary dysplasia.

Genes 15:806 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (Adm), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the molecular and cellular mechanisms through which Adm influences BPD pathogenesis using a lipopolysaccharide (LPS)-induced model of experimental BPD in mice. Bulk RNA sequencing of Adm-sufficient (wild-type or Adm+/+) and Adm-haplodeficient (Adm+/-) mice lungs, integrated with single-cell RNA sequencing data, revealed distinct gene expression patterns and cell type alterations associated with Adm deficiency and LPS exposure. Notably, computational integration with cell atlas data revealed that Adm-haplodeficient mouse lungs exhibited gene expression signatures characteristic of increased inflammation, natural killer (NK) cell frequency, and decreased endothelial cell and type II pneumocyte frequency. Furthermore, in silico human BPD patient data analysis supported our cell type frequency finding, highlighting elevated NK cells in BPD infants. These results underscore the protective role of Adm in experimental BPD and emphasize that it is a potential therapeutic target for BPD infants with an inflammatory phenotype.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Rna-seq ; Adrenomedullin ; Bronchopulmonary Dysplasia ; Natural Killer Cells; Branching Morphogenesis; Lung Angiogenesis; Care Practices; Mice Lacking; Risk-factors; Cell Atlas; Preterm; Expression; Hyperoxia; Outcomes
ISSN (print) / ISBN 2073-4425
e-ISSN 2073-4425
Zeitschrift Genes
Quellenangaben Band: 15, Heft: 6, Seiten: , Artikelnummer: 806 Supplement: ,
Verlag MDPI
Verlagsort St Alban-anlage 66, Ch-4052 Basel, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen NIH
Genomic and RNA Profiling Core at Baylor College of Medicine
National Institutes of Science Grant