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Isoform-Specific Modulation of Inflammation Induced by Adenoviral Mediated Delivery of Platelet-Derived Growth Factors in the Adult Mouse Heart
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden..
Univ Kuopio, Dept Biotechnol & Mol Med, Al Virtanen Inst Mol Sci, Kuopio, Finland..
Univ Kuopio, Dept Biotechnol & Mol Med, Al Virtanen Inst Mol Sci, Kuopio, Finland..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden..
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 8, e0160930Article in journal (Refereed) Published
Abstract [en]

Platelet-derived growth factors (PDGFs) are key regulators of mesenchymal cells in vertebrate development. To what extent PDGFs also exert beneficial homeostatic or reparative roles in adult organs, as opposed to adverse fibrogenic responses in pathology, are unclear. PDGF signaling plays critical roles during heart development, during which forced overexpression of PDGFs induces detrimental cardiac fibrosis; other studies have implicated PDGF signaling in post-infarct myocardial repair. Different PDGFs may exert different effects mediated through the two PDGF receptors (PDGFR alpha and PDGFR beta) in different cell types. Here, we assessed responses induced by five known PDGF isoforms in the adult mouse heart in the context of adenovirus vector-mediated inflammation. Our results show that different PDGFs have different, in some cases even opposing, effects. Strikingly, whereas the major PDGFRa agonists (PDGF-A and -C) decreased the amount of scar tissue and increased the numbers of PDGFR alpha-positive fibroblasts, PDGFR beta agonists either induced large scars with extensive inflammation (PDGF-B) or dampened the adenovirusinduced inflammation and produced a small and dense scar (PDGF-D). These results provide evidence for PDGF isoform-specific inflammation-modulating functions that may have therapeutic implications. They also illustrate a surprising complexity in the PDGF-mediated pathophysiological responses.

Place, publisher, year, edition, pages
2016. Vol. 11, no 8, e0160930
National Category
Immunology in the medical area Cell and Molecular Biology Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-304217DOI: 10.1371/journal.pone.0160930ISI: 000381381100090PubMedID: 27513343OAI: oai:DiVA.org:uu-304217DiVA: diva2:1048274
Funder
Swedish Cancer SocietySwedish Research CouncilKnut and Alice Wallenberg FoundationTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseThe Karolinska Institutet's Research Foundation
Note

Radiosa Gallini and Jenni Huusko contributed equally to this work.

Available from: 2016-11-21 Created: 2016-10-03 Last updated: 2016-11-23Bibliographically approved

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