In addition, we demonstrated for the first time that FGFR4 is upregulated in heart tissue of kl/kl mice and this resulted in activation of calcineurin/NFAT signaling and finally induction of pro-hypertrophic NFAT target genes Rcan1, bMHC, ANP, and BNP. Furthermore, kl/kl mice further displayed enhanced myocardial fibrosis with concomitant induction of collagen 1, Mmp2 and Tgf-β1 expression, activated ERK1/2 and Ctgf protein. This evidence concerns the gene CCN2 and Myocardial fibrosis.