| First Author | Gallini R | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 8 | Pages | e0160930 |
| PubMed ID | 27513343 | Mgi Jnum | J:254438 |
| Mgi Id | MGI:6099899 | Doi | 10.1371/journal.pone.0160930 |
| Citation | Gallini R, et al. (2016) Isoform-Specific Modulation of Inflammation Induced by Adenoviral Mediated Delivery of Platelet-Derived Growth Factors in the Adult Mouse Heart. PLoS One 11(8):e0160930 |
| abstractText | 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 (PDGFRalpha and PDGFRbeta) 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 PDGFRalpha agonists (PDGF-A and -C) decreased the amount of scar tissue and increased the numbers of PDGFRalpha-positive fibroblasts, PDGFRbeta agonists either induced large scars with extensive inflammation (PDGF-B) or dampened the adenovirus-induced 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. |
