Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Biasin, V; Crnkovic, S; Sahu-Osen, A; Birnhuber, A; El Agha, E; Sinn, K; Klepetko, W; Olschewski, A; Bellusci, S; Marsh, LM; Kwapiszewska, G.
PDGFRα and αSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis.
Am J Physiol Lung Cell Mol Physiol. 2020; 318(4):L684-L697
Doi: 10.1152/ajplung.00128.2019
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- Führende Autor*innen der Med Uni Graz
- Biasin Valentina
- Kwapiszewska-Marsh Grazyna
- Co-Autor*innen der Med Uni Graz
- Birnhuber Anna
- Crnkovic Slaven
- Marsh Leigh
- Olschewski Andrea
- Sahu-Osen Anita
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- Abstract:
- Pulmonary fibrosis is characterized by pronounced collagen deposition and myofibroblast expansion, whose origin and plasticity remain elusive. We utilized a fate-mapping approach to investigate α-smooth muscle actin (αSMA)+ and platelet-derived growth factor receptor α (PDGFRα)+ cells in two lung fibrosis models, complemented by cell type-specific next-generation sequencing and investigations on human lungs. Our data revealed that αSMA+ and PDGFRα+ cells mark two distinct mesenchymal lineages with minimal transdifferentiation potential during lung fibrotic remodeling. Parenchymal and perivascular fibrotic regions were populated predominantly with PDGFRα+ cells expressing collagen, while αSMA+ cells in the parenchyma and vessel wall showed variable expression of collagen and the contractile protein desmin. The distinct gene expression profile found in normal conditions was retained during pathologic remodeling. Cumulatively, our findings identify αSMA+ and PDGFRα+ cells as two separate lineages with distinct gene expression profiles in adult lungs. This cellular heterogeneity suggests that anti-fibrotic therapy should target diverse cell populations.
- Find related publications in this database (Keywords)
- collagen
- fibroblasts
- fibrosis
- myofibroblasts
- transdifferentiation