The Role of Pericytes in Lipopolysaccharide-Induced Murine Acute Respiratory Distress Syndrome.
Am J Pathol
; 194(8): 1443-1457, 2024 08.
Article
en En
| MEDLINE
| ID: mdl-38705380
ABSTRACT
Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome that is most commonly triggered by infection-related inflammation. Lung pericytes can respond to infection and act as immune and proangiogenic cells; moreover, these cells can differentiate into myofibroblasts in nonresolving ARDS and contribute to the development of pulmonary fibrosis. Here, we aimed to characterize the role of lung cells, which present characteristics of pericytes, such as peri-endothelial location and expression of a panel of specific markers. A murine model of lipopolysaccharide (LPS)-induced resolving ARDS was used to study their role in ARDS. The development of ARDS was confirmed after LPS instillation, which was resolved 14 days after onset. Immunofluorescence and flow cytometry showed early expansion of neural-glial antigen 2+ ß-type platelet-derived growth factor receptor+ pericytes in murine lungs with loss of CD31+ ß-type platelet-derived growth factor receptor+ endothelial cells. These changes were accompanied by specific changes in lung structure and loss of vascular integrity. On day 14 after ARDS onset, the composition of pericytes and endothelial cells returned to baseline values. LPS-induced ARDS activated NOTCH signaling in lung pericytes, the inhibition of which during LPS stimulation reduced the expression of its downstream target genes, pericyte markers, and angiogenic factors. Together, these data indicate that lung pericytes in response to inflammatory injury activate NOTCH signaling that supports their maintenance and in turn can contribute to recovery of the microvascular endothelium.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Síndrome de Dificultad Respiratoria
/
Lipopolisacáridos
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Pericitos
Límite:
Animals
Idioma:
En
Revista:
Am J Pathol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Polonia