NO-sensitive guanylyl cyclase discriminates pericyte-derived interstitial from intra-alveolar myofibroblasts in murine pulmonary fibrosis.
Respir Res
; 24(1): 167, 2023 Jun 22.
Article
em En
| MEDLINE
| ID: mdl-37349733
ABSTRACT
BACKGROUND:
The origin of αSMA-positive myofibroblasts, key players within organ fibrosis, is still not fully elucidated. Pericytes have been discussed as myofibroblast progenitors in several organs including the lung.METHODS:
Using tamoxifen-inducible PDGFRß-tdTomato mice (PDGFRß-CreERT2; R26tdTomato) lineage of lung pericytes was traced. To induce lung fibrosis, a single orotracheal dose of bleomycin was given. Lung tissue was investigated by immunofluorescence analyses, hydroxyproline collagen assay and RT-qPCR.RESULTS:
Lineage tracing combined with immunofluorescence for nitric oxide-sensitive guanylyl cyclase (NO-GC) as marker for PDGFRß-positive pericytes allows differentiating two types of αSMA-expressing myofibroblasts in murine pulmonary fibrosis (1) interstitial myofibroblasts that localize in the alveolar wall, derive from PDGFRß+ pericytes, express NO-GC and produce collagen 1. (2) intra-alveolar myofibroblasts which do not derive from pericytes (but express PDGFRß de novo after injury), are negative for NO-GC, have a large multipolar shape and appear to spread over several alveoli within the injured areas. Moreover, NO-GC expression is reduced during fibrosis, i.e., after pericyte-to-myofibroblast transition.CONCLUSION:
In summary, αSMA/PDGFRß-positive myofibroblasts should not be addressed as a homogeneous target cell type within pulmonary fibrosis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Respir Res
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Alemanha