NO-sensitive Guanylyl Cyclase Discriminates Pericyte-derived Interstitial from Intra-alveolar Myofibroblasts in Murine Pulmonary Fibrosis

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2023 Jun 22

PMID 37349733

Authors

Annemarie Aue

Nils Englert

Leon Harrer

Fabian Schwiering

Annika Gaab

Peter Konig

Ralf Adams

Achim Schmidtko

Andreas Friebe

Dieter Groneberg

Affiliations

Soon will be listed here.

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 PDGFRβ-tdTomato mice (PDGFRβ-CreER; 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 PDGFRβ-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 PDGFRβ pericytes, express NO-GC and produce collagen 1. (2) intra-alveolar myofibroblasts which do not derive from pericytes (but express PDGFRβ 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/PDGFRβ-positive myofibroblasts should not be addressed as a homogeneous target cell type within pulmonary fibrosis.

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