ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
Pericyte-like cells undergo transcriptional reprogramming and distinct functional adaptations in acute lung injury.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Lung Pericytes: Molecular Mechanisms, Signaling Pathways, and Roles in Pulmonary Diseases.Comprehensive Physiology · 2026Review
- Conditional BCL-2 Expression in Fibroblasts Promotes Persistent Pulmonary Fibrosis which is Reversible by Therapeutic BCL-2 Inhibition.Nature communications · 2026Article
- FOXF2 regulates pericyte-endothelial signaling required for vascular homeostasis after neonatal hyperoxic lung injury.Nature communications · 2026Article
- The Novel Soluble Guanylate Cyclase Stimulator Attenuates Acute Lung Injury via Inhibiting Pericyte Phenotypic Transition.International journal of molecular sciences · 2026Article
- Conserved stromal EMT program controls regenerative capacity of mesenchymal stromal cells across multiple tissues.Science advances · 2026Article
- Pericytes and Lung Vascular Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Review
- Review
- The role of cardiac pericytes in health and disease: therapeutic targets for myocardial infarction.Nature reviews. Cardiology · 2024Review
- Lung pericytes as mediators of inflammation.American journal of physiology. Lung cellular and molecular physiology · 2023Review
- New Insights into the Alveolar Epithelium as a Driver of Acute Respiratory Distress Syndrome.Biomolecules · 2022Review
- Effect of lung pericyte-like cell ablation on the bleomycin model of injury and repair.American journal of physiology. Lung cellular and molecular physiology · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We previously reported on the role of pericyte-like cells as functional sentinel immune cells in lung injury. However, much about the biological role of pericytes in lung injury remains unknown. Lung pericyte-like cells are well-positioned to sense disruption to the epithelial barrier and coordinate local inflammatory responses due to their anatomic niche within the alveoli. In this report, we characterized transcriptional responses and functional changes in pericyte-like cells following activation by alveolar components from injured and uninjured lungs in a mouse model of acute lung injury (ALI). Purified pericyte-like cells from lung digests using PDGFRβ as a selection marker were expanded in culture as previously described (1). We induced sterile acute lung injury in mice with recombinant human Fas ligand (rhFasL) instillation followed by mechanical ventilation (1). We then collected bronchoalveolar lavage fluid (BALF) from injured and uninjured mice. Purified pericyte-like cells in culture were exposed to growth media only (control), BALF from uninjured mice, and BALF from injured mice for 6 and 24 hours. RNA collected from these treatment conditions were processed for RNAseq. Targets of interest identified by pathway analysis were validated using in vitro and in vivo assays. We observed robust global transcriptional changes in pericyte-like cells following treatment with uninjured and injured BALF at 6 hours, but this response persisted for 24 hours only after exposure to injured BALF. Functional enrichment analysis of pericytes treated with injured BALF revealed the activation of pro-inflammatory, cell migration, and angiogenesis-related pathways, whereas processes associated with tissue development and cell differentiation were down-regulated. We validated select upregulated targets in the inflammatory, angiogenic, and cell migratory pathways using functional biological assays in vitro and in vivo. We conclude that lung pericyte-like cells are highly responsive to alveolar compartment content from both uninjured and injured lungs, but injured BALF elicits a more sustained response. The inflammatory, angiogenic, and migratory changes exhibited by activated pericyte-like cells underscore the phenotypic plasticity of these specialized stromal cells in the setting of acute lung injury.
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