Cell type-specific expression of angiotensin receptors in the human lung with implications for health, aging, and chronic disease.

Autor: Benjamin KJ; Lieber Institute for Brain Development, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Sauler M; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Poonyagariyagorn H; Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Neptune ER; Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 22. Date of Electronic Publication: 2024 Jun 22.
DOI: 10.1101/2024.06.17.599425
Abstrakt: The renin-angiotensin system is a highly characterized integrative pathway in mammalian homeostasis whose clinical spectrum has been expanded to lung disorders such as chronic obstructive pulmonary disease (COPD)-emphysema, idiopathic pulmonary fibrosis (IPF), and COVID pathogenesis. Despite this widespread interest, specific localization of this receptor family in the mammalian lung is limited, partially due to the imprecision of available antibody reagents. In this study, we establish the expression pattern of the two predominant angiotensin receptors in the human lung, AGTR1 and AGTR2 , using complementary and comprehensive bulk and single-cell RNA-sequence datasets that are publicly available. We show these two receptors have distinct localization patterns and developmental trajectories in the human lung, pericytes for AGTR1 and a subtype of alveolar epithelial type 2 cells for AGTR2 . In the context of disease, we further pinpoint AGTR2 localization to the COPD-associated subpopulation of alveolar epithelial type 2 (AT2 B ) and AGTR1 localization to fibroblasts, where their expression is upregulated in individuals with COPD, but not in individuals with IPF. Finally, we examine the genetic variation of the angiotensin receptors, finding AGTR2 associated with lung phenotype (i.e., cystic fibrosis) via rs1403543. Together, our findings provide a critical foundation for delineating this pathway's role in lung homeostasis and constructing rational approaches for targeting specific lung disorders.
Competing Interests: Competing interest The authors declare no competing interests.
Databáze: MEDLINE
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