NO-sensitive guanylyl cyclase discriminates pericyte-derived interstitial from intra-alveolar myofibroblasts in murine pulmonary fibrosis
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-357805
- 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-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 LineageBackground 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-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 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.…
Autor(en): | Annemarie Aue, Nils Englert, Leon Harrer, Fabian Schwiering, Annika Gaab, Peter König, Ralf Adams, Achim Schmidtko, Andreas Friebe, Dieter Groneberg |
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URN: | urn:nbn:de:bvb:20-opus-357805 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Physiologisches Institut |
Medizinische Fakultät / Klinik und Poliklinik für Anästhesiologie (ab 2004) | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Respiratory Research |
Erscheinungsjahr: | 2023 |
Band / Jahrgang: | 24 |
Aufsatznummer: | 167 |
Originalveröffentlichung / Quelle: | Respiratory Research (2023) 24:167. https://doi.org/10.1186/s12931-023-02479-2 |
DOI: | https://doi.org/10.1186/s12931-023-02479-2 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 612 Humanphysiologie | |
Freie Schlagwort(e): | fibrosis; guanylyl cyclase; myofibroblasts; pericytes; transgenic mouse |
Datum der Freischaltung: | 21.05.2024 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |