TY  - JOUR
A1  - Aue, Annemarie
A1  - Englert, Nils
A1  - Harrer, Leon
A1  - Schwiering, Fabian
A1  - Gaab, Annika
A1  - König, Peter
A1  - Adams, Ralf
A1  - Schmidtko, Achim
A1  - Friebe, Andreas
A1  - Groneberg, Dieter
T1  - NO-sensitive guanylyl cyclase discriminates pericyte-derived interstitial from intra-alveolar myofibroblasts in murine pulmonary fibrosis
T2  - Respiratory Research
N2  - 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
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.
KW  - guanylyl cyclase
KW  - myofibroblasts
KW  - pericytes
KW  - transgenic mouse
KW  - fibrosis
Y1  - 2023
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/35780
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-357805
VL  - 24
ER  -