NO-sensitive guanylyl cyclase discriminates pericyte-derived interstitial from intra-alveolar myofibroblasts in murine pulmonary fibrosis

Respiratory Research

Research

Peter König¹  Achim Schmidtko²  Ralf Adams³  Fabian Schwiering⁴  Annika Gaab⁴  Andreas Friebe⁴  Dieter Groneberg⁴  Nils Englert⁴  Leon Harrer⁴  Annemarie Aue⁵ 

[1] Institut für Anatomie, Zentrum für Medizinische Struktur- und Zellbiologie, Universität zu Lübeck, 23562, Lübeck, Germany;Airway Research Center North (ARCN), German Center for Lung Research (DZL), Giessen, Germany;Institut für Pharmakologie und Klinische Pharmazie, Goethe-Universität Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany;Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, Faculty of Medicine, University of Münster, 48149, Münster, Germany;Physiologisches Institut, Julius-Maximilians-Universität Würzburg, Röntgenring 9, 97070, Würzburg, Germany;Physiologisches Institut, Julius-Maximilians-Universität Würzburg, Röntgenring 9, 97070, Würzburg, Germany;Zentrum für Interdisziplinäre Schmerzmedizin, Klinik für Anästhesiologie Intensivmedizin, Notfallmedizin und Schmerztherapie, Universitätsklinikum Würzburg, 97080, Würzburg, Germany;

关键词: Guanylyl cyclase;    Myofibroblasts;    Pericytes;    Transgenic mouse;    Fibrosis;   

DOI  :  10.1186/s12931-023-02479-2

 received in 2022-12-21, accepted in 2023-06-14,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsUsing tamoxifen-inducible PDGFRβ-tdTomato mice (PDGFRβ-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.ResultsLineage 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.ConclusionIn summary, αSMA/PDGFRβ-positive myofibroblasts should not be addressed as a homogeneous target cell type within pulmonary fibrosis.

【 授权许可】

CC BY   
© The Author(s) 2023

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