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Isoform-Specific Mo...
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Gallini, RadiosaUppsala universitet,Molekylära verktyg,Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden.
(author)
Isoform-Specific Modulation of Inflammation Induced by Adenoviral Mediated Delivery of Platelet-Derived Growth Factors in the Adult Mouse Heart
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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2016-08-11
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Public Library of Science (PLoS),2016
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-304217
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-304217URI
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https://doi.org/10.1371/journal.pone.0160930DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:134151704URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Radiosa Gallini and Jenni Huusko contributed equally to this work.
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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.
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Huusko, JenniUniv Kuopio, Dept Biotechnol & Mol Med, Al Virtanen Inst Mol Sci, Kuopio, Finland.
(author)
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Yla-Herttuala, SeppoUniv Kuopio, Dept Biotechnol & Mol Med, Al Virtanen Inst Mol Sci, Kuopio, Finland.
(author)
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Betsholtz, ChristerKarolinska Institutet,Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden.(Swepub:uu)chbet517
(author)
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Andrae, JohannaUppsala universitet,Vaskulärbiologi(Swepub:uu)johaandr
(author)
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Uppsala universitetMolekylära verktyg
(creator_code:org_t)
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In:PLOS ONE: Public Library of Science (PLoS)11:81932-6203
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