PDGFRα and αSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis

doi:10.1152/ajplung.00128.2019

. 2020 Apr 1;318(4):L684-L697.

doi: 10.1152/ajplung.00128.2019. Epub 2020 Feb 5.

PDGFRα and αSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis

Valentina Biasin^{1

2}, Slaven Crnkovic^{2

3}, Anita Sahu-Osen², Anna Birnhuber², Elie El Agha⁴, Katharina Sinn⁵, Walter Klepetko⁵, Andrea Olschewski^{2

6}, Saverio Bellusci⁴, Leigh M Marsh², Grazyna Kwapiszewska^{2

3}

Affiliations

¹ Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
² Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
³ Otto Loewi Research Center, Division of Physiology, Medical University of Graz, Graz, Austria.
⁴ Excellence Cluster Cardio-Pulmonary System (ECCPS), Member of the German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University Giessen, Giessen, Germany.
⁵ Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Austria.
⁶ Experimental Anesthesiology, Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

PMID: 32023084
PMCID: PMC7189793
DOI: 10.1152/ajplung.00128.2019

PDGFRα and αSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis

Valentina Biasin et al. Am J Physiol Lung Cell Mol Physiol. 2020.

. 2020 Apr 1;318(4):L684-L697.

doi: 10.1152/ajplung.00128.2019. Epub 2020 Feb 5.

Authors

Affiliations

¹ Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
² Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
³ Otto Loewi Research Center, Division of Physiology, Medical University of Graz, Graz, Austria.
⁴ Excellence Cluster Cardio-Pulmonary System (ECCPS), Member of the German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center (UGMLC), Justus Liebig University Giessen, Giessen, Germany.
⁵ Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Austria.
⁶ Experimental Anesthesiology, Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

PMID: 32023084
PMCID: PMC7189793
DOI: 10.1152/ajplung.00128.2019

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.

Keywords: collagen; fibroblasts; fibrosis; myofibroblasts; transdifferentiation.

PubMed Disclaimer

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

**Fig. 1.**
α-Smooth muscle actin (αSMA)- and platelet-derived growth factor receptor-α (PDGFRα)-expressing cells represent two distinct populations of fibroblasts in human idiopathic pulmonary fibrosis (IPF) lungs. A: immunofluorescence staining of human donor and IPF sections for αSMA, PDGFRα, and von Willebrand factor (vWF). Parenchymal and vascular regions are shown. Scale bar: overview 200 µm; single staining and merged 50 µm; zoomed merged 12.5 µm. Arrows: single αSMA-positive cells; arrowheads: single PDGFRα-positive cells; asterisk: double αSMA/PDGFRα-positive cells. Number and percentage of positive cells for single αSMA, single PDGFRα, and double αSMA/PDGFRα-positive cells in the parenchyma (B) and in the vasculature (C). Cell counts were performed on 3–5 images for each donor and IPF section from n = 6–8 different donors and IPF lungs. P < 0.05 was considered significant. #Differences between single PDGFRα-positive cells in IPF compared with donor lungs. D: t-distributed stochastic neighbor embedding (tSNE) plots showing expression of ACTA2 and PDGFRA expression on the fibroblasts cluster. Data from Reyfman et al. data set (GSE122960) (25).

**Fig. 2.**
Both α-smooth muscle actin (αSMA)- and platelet-derived growth factor receptor-α (PDGFRα)-expressing cells contribute to collagen production, but desmin (DES) is expressed mostly by αSMA-expressing cells in human idiopathic pulmonary fibrosis (IPF) lungs. A: multicolor immunofluorescence staining of human donor and IPF sections for αSMA, PDGFRα, and collagen 1 (COL1). Parenchymal and vascular regions are shown. Scale bar: merged 50 µm; zoomed 12.5 µm. Arrows: single αSMA-positive cells; arrowheads: single PDGFRα-positive cells; asterisk: double αSMA/COL1 or PDGFRα/COL1-positive cells. Number and percentage of single αSMA, single PDGFRα, double αSMA /COL1, and double PDGFRα /COL1-positive cells in the parenchyma (B) and in the vasculature (C). Cell count was performed on 3–6 images for each donor and IPF section from n = 3–4 different donors and IPF lungs. P value < 0.05 was considered significant. $Differences between double PDGFRα/COL1-positive cells in IPF compared with donor lungs. D: multicolor immunofluorescence staining of human donor and IPF sections for αSMA, PDGFRα, and DES. Parenchymal and vascular region are shown. Scale bar: merged 50 µm; zoomed merged 12.5 µm. Arrows: single αSMA-positive cells; arrowheads: single PDGFRα-positive cells; asterisk: double αSMA/DES or PDGFRα/DES-positive cells. Number and percentage of single αSMA, single PDGFRα, double αSMA/DES, and double PDGFRα/DES-positive cells in the parenchyma (E) and in the vasculature (F). Cell count was performed in 3–6 images for each donor and IPF section from n = 2–3 different donors and IPF. P value < 0.05 was considered significant. #Differences between single PDGFRα-positive cells in IPF compared with donor lungs.

**Fig. 3.**
Lineage-traced α-smooth muscle actin (αSMA)-expressing cells contribute to parenchymal and vascular remodeling in bleomycin model. A: lineage tracing of αSMA-positive cells (*Acta2-tdT*) and immunofluorescence staining for platelet-derived growth factor receptor-α (PDGFRα) and von Willebrand factor (vWF) was performed in saline- and bleomycin-treated mice. Parenchymal and vascular regions are shown. Scale bar: overview 200 µm; single staining and merged 50 µm; zoomed merged 12.5 µm. Arrows: single *Acta-tdT*-positive cells; arrowheads: single PDGFRα-positive cells; asterisk: double *Acta-tdT*/PDGFRα-positive cells. Number and percentage of *Acta2-tdT* and PDGFRα-positive cells in the parenchyma (B) and in the vasculature (C). Cell count was performed in 3–8 images for each mouse section from n = 3–4 different saline- and bleomycin-treated mice. P value < 0.05 was considered significant. #Differences between single PDGFRα-positive cells; *Differences between single *Acta2-tdT* positive cells in bleomycin- compared with saline-treated mice.

**Fig. 4.**
Lineage-traced α-smooth muscle actin (αSMA)-expressing cells contribute to parenchymal and vascular remodeling in *Fra-2 Tg* mice. A: lineage tracing of αSMA-positive cells (*Acta2-tdT*) and immunofluorescence staining for platelet-derived growth factor receptor-α (PDGFRα) and von Willebrand factor (vWF) was performed in wild-type (wt) littermates and *Fra-2 tg* mice. Parenchymal and vascular regions are shown. Scale bar: overview 200 µm; single staining and merged 50 µm; zoomed merged 12.5 µm. Arrows: single *Acta2-tdT*-positive cells; arrowheads: single PDGFRα-positive cells; asterisk: double *Acta2-tdT* /PDGFRα-positive cells. Number and percentage of single *Acta2-tdT*, single PDGFRα and *Acta2-tdT*/PDGFRα double positive cells in the parenchyma (B) and in the vasculature (C). Cell count was performed in 4–9 images for each mouse section from n = 3–5 different wt littermate controls and *Fra-2 Tg* mice. P value < 0.05 was considered significant. #Differences between single PDGFRα-positive cells in *Fra-2 Tg* mice compared with wt littermates.

**Fig. 5.**
Lineage-traced platelet-derived growth factor receptor-α (PDGFRα)-positive cells strongly contribute to parenchymal remodeling in bleomycin model. A: lineage tracing of PDGFRα-positive cells (*Pdgfra-tdT*) and immunofluorescence staining for α-smooth muscle actin (αSMA) and von Willebrand factor (vWF) was performed in saline- and bleomycin-treated mice. Parenchymal and vascular regions are shown. Scale bar: overview 200 µm; single staining and merged 50 µm; zoomed merged 12.5 µm. Arrows: single αSMA-positive cells; arrowheads: single *Pdgfra-tdT*-positive cells; asterisk: double αSMA/ *Pdgfra-tdT*-positive cells. Number and percentage of single αSMA, single *Pdgfra-tdT*, and αSMA/*Pdgfra-tdT* double positive cells in the parenchyma (B) and in the vasculature (C). Cell count was performed in 6–10 images for each mouse section from n = 3–5 different saline- and bleomycin-treated mice. P value < 0.05 was considered significant.

**Fig. 6.**
Lineage-traced platelet-derived growth factor receptor-α (PDGFRα)-positive cells partially contribute to parenchymal remodeling in Fra-2 Tg mice. Lineage tracing of PDGFRα-positive cells (*Pdgfra-tdT*) and immunofluorescence staining for α-smooth muscle actin (αSMA) and von Willebrand factor (vWF) was performed in wild-type (wt) littermates and *Fra-2 Tg* mice A: parenchymal and vascular regions are shown. Scale bar: overview 200 µm; single staining and merged 50 µm; zoomed merged 12.5 µm. Arrows: single αSMA-positive cells; arrowheads: single *Pdgfra-tdT*-positive cells; asterisk: double αSMA/*Pdgfra-tdT*-positive cells. Number and percentage of single αSMA, single *Pdgfra-tdT*, and αSMA/*Pdgfra-tdT* double positive cells in the parenchyma (B) and in the vasculature (C). Cell count was performed in 6–10 images for each mouse section from n = 4 different littermate controls and *Fra-2 Tg mice*. P value < 0.05 was considered significant. #Differences between single *Pdgfra-tdT*-positive cells; *differences between single αSMA-positive cells in *Fra-2 Tg* mice compared with wt littermates.

**Fig. 7.**
α-Smooth muscle actin (αSMA)- and platelet-derived growth factor receptor-α (PDGFRα)-expressing cells present a distinct gene expression. *A, D, G, J*: schematic representation of the applied workflow for RNA sequencing. *B, E, H, K*: principal component analysis (PCA) of the normalized RNA-Seq data transcripts of the reported groups. *C, F, I, L*: heatmap of hierarchical clustering showing the top 30 differentially expressed protein-coding genes between the reported groups.

**Fig. 8.**
A fraction of both α-smooth muscle actin (αSMA) and platelet-derived growth factor receptor-α (PDGFRα)-positive cells express collagen 1 (COL1), while desmin (DES) is expressed mostly by αSMA-expressing cells in bleomycin. A: lineage tracing of PDGFRα-positive cells (*Pdgfra-tdT*) and immunofluorescence staining for αSMA and COL1 in saline- and bleomycin-treated mice. Parenchymal and vascular regions are shown. Scale bar: single staining and merged 50 µm; zoomed merged 12.5 µm. Arrows: single αSMA-positive cells; arrowheads: single *Pdgfra-tdT*-positive cells; asterisk: double αSMA/COL1 or *Pdgfra-tdT*/COL1-positive cells. Number and percentage of single αSMA, single *Pdgfra-tdT*, αSMA/COL1 and *Pdgfra-tdT* /COL1 double positive cells in the parenchyma (B) and in the vasculature (C). P value < 0.05 was considered significant. #Differences between single *Pdgfra-tdT* positive cells in bleomycin compared with saline. D: lineage tracing of PDGFRα-positive cells (*Pdgfra-tdT*) and immunofluorescence staining for αSMA and DES in saline- and bleomycin-treated mice. Parenchymal and vascular region are shown. Scale bar: merged 50 µm; zoomed merged 12.5 µm. Arrows: single αSMA-positive cells; arrowheads: single PDGFRα-positive cells; asterisk: double αSMA/DES or PDGFRα/DES-positive cells. Number and percentage of αSMA, *Pdgfra-tdT*, αSMA/DES, and *Pdgfra-tdT* /DES double positive cells in the parenchyma (E) and in the vasculature (F). P value < 0.05 was considered significant. #Differences between single *Pdgfra-tdT*-positive cells; *differences between single αSMA-positive cells in bleomycin compared with saline treatment. G: t-distributed stochastic neighbor embedding (tSNE) plots showing expression of Acta2, Pdgfra, Col1a1, and Des on the fibroblasts cluster upon saline and bleomycin treatment. Data from the Peyser et al. data set (GSE129605) (23).

**Fig. 9.**
A fraction of both α-smooth muscle actin (αSMA)- and platelet-derived growth factor receptor-α (PDGFRα)-positive cells express collagen 1 (COL1), while desmin (DES) is expressed mostly by αSMA-expressing cells in *Fra-2 Tg* mice. A: lineage tracing of PDGFRα-positive cells (*Pdgfra-tdT*) and immunofluorescence staining for αSMA and COL1 in wild-type (wt) littermates and *Fra-2 Tg* mice. Parenchymal and vascular regions are shown. Scale bar: merged 50 µm; zoomed merged 12.5 µm. Arrows: single αSMA-positive cells; arrowheads: single PDGFRα-positive cells; asterisk: double αSMA/COL1 or PDGFRα/COL1-positive cells. Number and percentage of single αSMA, single *Pdgfra-tdT*, αSMA/COL1, and *Pdgfra-tdT*/COL1 double positive cells in the parenchyma (B) and in the vasculature (C). P value < 0.05 was considered significant. *Differences between single αSMA-positive cells in *Fra-2 Tg* mice compared with wt littermates. Cell count was performed in 3–5 images for mouse section from n = 2–3 different littermate controls and *Fra-2 Tg* mice. D: lineage tracing of PDGFRα cells (*Pdgfra-tdT*) and immunofluorescence staining for αSMA and DES in wt littermates and *Fra-2 Tg* mice. Parenchymal and vascular regions are shown. Scale bar: merged 50 µm; zoomed merged 12.5 µm. Arrows: single αSMA-positive cells; arrowheads: single *Pdgfra-tdT*-positive cells; asterisk: double αSMA/DES or *Pdgfra-tdT*/DES-positive cells. Number and percentage of αSMA, *Pdgfra-tdT* single positive, αSMA/DES, and *Pdgfra-tdT*/DES double positive cells in the parenchyma (E) and in the vasculature (F). P value < 0.05 was considered significant. #Differences between single *Pdgfra-tdT*-positive cells; *differences between single αSMA-positive cells; $difference between double αSMA/DES-positive cells in *Fra-2 Tg* mice compared with wt littermates. Cell count was performed in 3–6 images for mouse section. n = 3–4 different littermate controls and *Fra-2 Tg* mice.

See this image and copyright information in PMC

Cited by

Understanding myofibroblast origin in the fibrotic lung.
Zabihi M, Shahriari Felordi M, Lingampally A, Bellusci S, Chu X, El Agha E. Zabihi M, et al. Chin Med J Pulm Crit Care Med. 2024 Sep 17;2(3):142-150. doi: 10.1016/j.pccm.2024.08.003. eCollection 2024 Sep. Chin Med J Pulm Crit Care Med. 2024. PMID: 39403408 Free PMC article. Review.
Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts.
Mayr CH, Sengupta A, Asgharpour S, Ansari M, Pestoni JC, Ogar P, Angelidis I, Liontos A, Rodriguez-Castillo JA, Lang NJ, Strunz M, Porras-Gonzalez D, Gerckens M, De Sadeleer LJ, Oehrle B, Viteri-Alvarez V, Fernandez IE, Tallquist M, Irmler M, Beckers J, Eickelberg O, Stoleriu GM, Behr J, Kneidinger N, Wuyts WA, Wasnick RM, Yildirim AÖ, Ahlbrecht K, Morty RE, Samakovlis C, Theis FJ, Burgstaller G, Schiller HB. Mayr CH, et al. Eur Respir J. 2024 Feb 8;63(2):2301326. doi: 10.1183/13993003.01326-2023. Print 2024 Feb. Eur Respir J. 2024. PMID: 38212077 Free PMC article.
Role of vascular smooth muscle cell clonality in atherosclerosis.
Luo L, Fu C, Bell CF, Wang Y, Leeper NJ. Luo L, et al. Front Cardiovasc Med. 2023 Nov 28;10:1273596. doi: 10.3389/fcvm.2023.1273596. eCollection 2023. Front Cardiovasc Med. 2023. PMID: 38089777 Free PMC article. Review.
The vascular perspective on acute and chronic lung disease.
Borek I, Birnhuber A, Voelkel NF, Marsh LM, Kwapiszewska G. Borek I, et al. J Clin Invest. 2023 Aug 15;133(16):e170502. doi: 10.1172/JCI170502. J Clin Invest. 2023. PMID: 37581311 Free PMC article. Review.
Optimized Protocol for Isolation and Culture of Murine Neonatal Primary Lung Fibroblasts.
Fuentes-Mateos R, Santos E, Fernández-Medarde A. Fuentes-Mateos R, et al. Methods Protoc. 2023 Jan 24;6(1):14. doi: 10.3390/mps6010014. Methods Protoc. 2023. PMID: 36827501 Free PMC article.

See all "Cited by" articles

References

1. Benayoun BA, Pollina EA, Singh PP, Mahmoudi S, Harel I, Casey KM, Dulken BW, Kundaje A, Brunet A. Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses. Genome Res 29: 697–709, 2019. doi:10.1101/gr.240093.118. - DOI - PMC - PubMed
1. Biasin V, Marsh LM, Egemnazarov B, Wilhelm J, Ghanim B, Klepetko W, Wygrecka M, Olschewski H, Eferl R, Olschewski A, Kwapiszewska G. Meprin β, a novel mediator of vascular remodelling underlying pulmonary hypertension. J Pathol 233: 7–17, 2014. doi:10.1002/path.4303. - DOI - PubMed
1. Biasin V, Wygrecka M, Marsh LM, Becker-Pauly C, Brcic L, Ghanim B, Klepetko W, Olschewski A, Kwapiszewska G. Meprin β contributes to collagen deposition in lung fibrosis. Sci Rep 7: 39969, 2017. doi:10.1038/srep39969. - DOI - PMC - PubMed
1. Birnhuber A, Biasin V, Schnoegl D, Marsh LM, Kwapiszewska G. Transcription factor Fra-2 and its emerging role in matrix deposition, proliferation and inflammation in chronic lung diseases. Cell Signal 64: 109408, 2019. doi:10.1016/j.cellsig.2019.109408. - DOI - PubMed
1. Birnhuber A, Crnkovic S, Biasin V, Marsh LM, Odler B, Sahu-Osen A, Stacher-Priehse E, Brcic L, Schneider F, Cikes N, Ghanim B, Klepetko W, Graninger W, Allanore Y, Eferl R, Olschewski A, Olschewski H, Kwapiszewska G. IL-1 receptor blockade skews inflammation towards Th2 in a mouse model of systemic sclerosis. Eur Respir J 54: 1900154, 2019. doi:10.1183/13993003.00154-2019. - DOI - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information
Molecular Biology Databases
- Mouse Genome Informatics (MGI)
Miscellaneous
- NCI CPTAC Assay Portal

[1] Benayoun BA, Pollina EA, Singh PP, Mahmoudi S, Harel I, Casey KM, Dulken BW, Kundaje A, Brunet A. Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses. Genome Res 29: 697–709, 2019. doi:10.1101/gr.240093.118. - DOI - PMC - PubMed

[2] Benayoun BA, Pollina EA, Singh PP, Mahmoudi S, Harel I, Casey KM, Dulken BW, Kundaje A, Brunet A. Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses. Genome Res 29: 697–709, 2019. doi:10.1101/gr.240093.118. - DOI - PMC - PubMed

[3] Biasin V, Marsh LM, Egemnazarov B, Wilhelm J, Ghanim B, Klepetko W, Wygrecka M, Olschewski H, Eferl R, Olschewski A, Kwapiszewska G. Meprin β, a novel mediator of vascular remodelling underlying pulmonary hypertension. J Pathol 233: 7–17, 2014. doi:10.1002/path.4303. - DOI - PubMed

[4] Biasin V, Marsh LM, Egemnazarov B, Wilhelm J, Ghanim B, Klepetko W, Wygrecka M, Olschewski H, Eferl R, Olschewski A, Kwapiszewska G. Meprin β, a novel mediator of vascular remodelling underlying pulmonary hypertension. J Pathol 233: 7–17, 2014. doi:10.1002/path.4303. - DOI - PubMed

[5] Biasin V, Wygrecka M, Marsh LM, Becker-Pauly C, Brcic L, Ghanim B, Klepetko W, Olschewski A, Kwapiszewska G. Meprin β contributes to collagen deposition in lung fibrosis. Sci Rep 7: 39969, 2017. doi:10.1038/srep39969. - DOI - PMC - PubMed

[6] Biasin V, Wygrecka M, Marsh LM, Becker-Pauly C, Brcic L, Ghanim B, Klepetko W, Olschewski A, Kwapiszewska G. Meprin β contributes to collagen deposition in lung fibrosis. Sci Rep 7: 39969, 2017. doi:10.1038/srep39969. - DOI - PMC - PubMed

[7] Birnhuber A, Biasin V, Schnoegl D, Marsh LM, Kwapiszewska G. Transcription factor Fra-2 and its emerging role in matrix deposition, proliferation and inflammation in chronic lung diseases. Cell Signal 64: 109408, 2019. doi:10.1016/j.cellsig.2019.109408. - DOI - PubMed

[8] Birnhuber A, Biasin V, Schnoegl D, Marsh LM, Kwapiszewska G. Transcription factor Fra-2 and its emerging role in matrix deposition, proliferation and inflammation in chronic lung diseases. Cell Signal 64: 109408, 2019. doi:10.1016/j.cellsig.2019.109408. - DOI - PubMed

[9] Birnhuber A, Crnkovic S, Biasin V, Marsh LM, Odler B, Sahu-Osen A, Stacher-Priehse E, Brcic L, Schneider F, Cikes N, Ghanim B, Klepetko W, Graninger W, Allanore Y, Eferl R, Olschewski A, Olschewski H, Kwapiszewska G. IL-1 receptor blockade skews inflammation towards Th2 in a mouse model of systemic sclerosis. Eur Respir J 54: 1900154, 2019. doi:10.1183/13993003.00154-2019. - DOI - PMC - PubMed

[10] Birnhuber A, Crnkovic S, Biasin V, Marsh LM, Odler B, Sahu-Osen A, Stacher-Priehse E, Brcic L, Schneider F, Cikes N, Ghanim B, Klepetko W, Graninger W, Allanore Y, Eferl R, Olschewski A, Olschewski H, Kwapiszewska G. IL-1 receptor blockade skews inflammation towards Th2 in a mouse model of systemic sclerosis. Eur Respir J 54: 1900154, 2019. doi:10.1183/13993003.00154-2019. - DOI - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

PDGFRα and αSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis

Affiliations

PDGFRα and αSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases

Miscellaneous

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases

Miscellaneous