Journal article
FGF23 activates injury-primed renal fibroblasts via FGFR4-dependent signalling and enhancement of TGF-β autoinduction
ER Smith, SG Holt, TD Hewitson
International Journal of Biochemistry and Cell Biology | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2017
Abstract
Bone-derived fibroblast growth factor 23 (FGF23) is an important endocrine regulator of mineral homeostasis with effects transduced by cognate FGF receptor (FGFR)1-α-Klotho complexes. Circulating FGF23 levels rise precipitously in patients with kidney disease and portend worse renal and cardiovascular outcomes. De novo expression of FGF23 has been found in the heart and kidney following injury but its significance remains unclear. Studies showing that exposure to chronically high FGF23 concentrations activates hypertrophic gene programs in the cardiomyocyte has spawned intense interest in other pathological off-target effects of FGF23 excess. In the kidney, observational evidence points to a..
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Funding Acknowledgements
We thank Belinda Wigg (RMH) for technical assistance with the cell culture studies, Mark Van der Hoek (David Gunn Genomics Facility, SAHMRI) who provided assistance with the NGS analyses and to TrendBio Pty Ltd who supplied some of the Viromer transfection reagents. The authors were supported by Project grant 1078694 from the National Health and Medical Research Council of Australia (NHMRC) and a Grant-in-Aid (GIA-021-2017) from the RMH Home Lottery Research Fund.