Sökning: WFRF:(Betsholtz Christer) > PDGF-A and PDGF-B i...
Fältnamn | Indikatorer | Metadata |
---|---|---|
000 | 03893naa a22006613a 4500 | |
001 | 20188375 | |
003 | SE-LIBR | |
005 | 20170322175937.0 | |
007 | cr|||||||||||| | |
008 | 170322s2016 sw |||| o |||| ||eng c | |
024 | 7 | a http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3120372 uri |
024 | 7 | a urn:nbn:se:uu:diva-3120372 urn |
024 | 7 | a 10.1016/j.yexcr.2016.10.0222 doi |
040 | a S | |
041 | 0 | a eng |
042 | 9 EPLK | |
100 | 1 | a Gallini, Radiosa4 aut |
245 | 1 0 | a PDGF-A and PDGF-B induces cardiac fibrosis in transgenic miceh [Elektronisk resurs] |
260 | c 2016 | |
500 | a Published | |
500 | a Cancerfonden | |
500 | a Vetenskapsrådet | |
500 | a Novo Nordisk | |
500 | a Knut och Alice Wallenbergs Stiftelse | |
500 | a Torsten Söderbergs stiftelse | |
500 | a Ragnar Söderbergs stiftelse | |
506 | 0 | a gratis |
520 | a Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) contribute to normal heart development. Deficient or abnormal expression of Pdgf and Pdgfr genes have a negative impact on cardiac development and function. The cellular effects of PDGFs in the hearts of Pdgf/Pdgfr mutants and the pathogenesis of the resulting abnormalities are poorly understood, but different PDGF isoforms induce varying effects. Here, we generated three new transgenic mouse types which complete a set of studies, where all different PDGF ligands have been expressed under the same heart specific alpha-myosin heavy chain promoter. Transgenic expression of the natural isoforms of Pdgfa and Pdgfb resulted in isoform specific fibrotic reactions and cardiac hypertrophy. Pdgfa overexpression resulted in a severe fibrotic reaction with up to 8-fold increase in cardiac size, leading to lethal cardiac failure within a few weeks after birth. In contrast, Pdgfb overexpression led to focal fibrosis and moderate cardiac hypertrophy. As PDGF-A and PDGF-B have different affinity for the two PDGF receptors, we analyzed the expression of the receptors and the histology of the fibrotic hearts. Our data suggest that the stronger fibrotic effect generated by Pdgfa overexpression was mediated by Pdgfra in cardiac interstitial mesenchymal cells, i.e. the likely source of extracellular matrix depostion and fibrotic reaction. The apparent sensitivity of the heart to ectopic PDGFR alpha agonists supports a role for endogenous PDGFRa agonists in the pathogenesis of cardiac fibrosis. | |
650 | 7 | a Medical and Health Sciences2 hsv |
650 | 7 | a Clinical Medicine2 hsv |
650 | 7 | a Cancer and Oncology2 hsv |
650 | 7 | a Medicin och hälsovetenskap2 hsv |
650 | 7 | a Klinisk medicin2 hsv |
650 | 7 | a Cancer och onkologi2 hsv |
650 | 7 | a Basic Medicine2 hsv |
650 | 7 | a Cell and Molecular Biology2 hsv |
650 | 7 | a Medicinska grundvetenskaper2 hsv |
650 | 7 | a Cell- och molekylärbiologi2 hsv |
653 | 0 | a PDGF |
653 | 0 | a Transgene |
653 | 0 | a Myosin heavy chain |
653 | 0 | a Fibrosis |
653 | 0 | a Heart |
700 | 1 | a Lindblom, Per4 aut |
700 | 1 | a Bondjers, Cecilia4 aut |
700 | 1 | a Betsholtz, Christer4 aut |
700 | 1 | a Andrae, Johanna4 aut |
710 | 1 2 | a Uppsala universitetb Medicinska och farmaceutiska vetenskapsområdet4 pbl |
710 | 1 2 | a Uppsala universitetb Medicinska och farmaceutiska vetenskapsområdet4 pbl |
772 | 1 8 | i channel recordw 19753896 |
773 | 0 8 | i Värdpublikationt Experimental Cell Researchg 349:2, 282-290x 0014-4827 |
856 | 4 0 | u http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-312037 |
856 | 4 0 | u http://dx.doi.org/10.1016/j.yexcr.2016.10.022 |
856 | 4 0 | u http://uu.diva-portal.org/smash/get/diva2:1062375/FULLTEXT01 |
841 | 5 APISa x ab 170322||0000|||||001||||||000000e 1 | |
024 | 7 | 5 APISa urn:nbn:se:uu:diva-3120372 urn |
852 | 5 APISb APIS | |
856 | 4 0 | 5 APISu http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-312037 |
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