Modification of alternative messenger RNA splicing of fibroblast growth factor receptors in human cardiac allografts during rejection

The Journal of Clinical Investigation
X M ZhaoG G Miller

Abstract

Accelerated coronary atherosclerosis in cardiac transplants (cardiac allograft vasculopathy, CAV) is characterized by coronary intimal hyperplasia. Acidic fibroblast growth factor (aFGF) is a potent mitogen for vascular smooth muscle cells and endothelial cells, and its expression is increased in cardiac allografts, suggesting it may play a role in the pathogenesis of CAV. The activity of aFGF is dependent on binding to transmembrane receptors. To investigate whether receptors for aFGF are also induced after transplantation, polymerase chain reaction, in situ hybridization, and immunohistochemistry were used to analyze expression of four receptors for aFGF (FGFR1-FGFR4). Expression of mRNA encoding extracellular immunoglobulin-like domains of FGFR1 was increased 35-fold in cardiac allografts compared with normal hearts and was predominantly present in cardiac myocytes and vascular structures. Alternatively spliced mRNA that encodes transmembrane forms of FGFR1, which contain the signal-transducing tyrosine kinase domains, was induced in allografts during rejection, in infiltrating cells, vascular structures, and myocytes. In vitro experiments showed that differential expression of FGF receptor isoforms was induced by aFGF, and ...Continue Reading

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Citations

Oct 19, 2000·Arthritis and Rheumatism·J W ThomasG G Miller
Apr 15, 2008·Trends in Endocrinology and Metabolism : TEM·S L Chew
Oct 13, 2011·The Journal of Biological Chemistry·Moonhee LeePatrick L McGeer
May 1, 1996·Clinical and Experimental Pharmacology & Physiology·A Agrotis, A Bobik
Jun 23, 1998·The Journal of Biological Chemistry·M M DikovG G Miller
Apr 10, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Wensheng LuoBarbara J Ballermann
Mar 7, 2003·The Journal of Biological Chemistry·Dawn M KilkennyGeraldine G Miller
Apr 9, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mengjie XiaoJunlian Gu

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