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• W2938369874 startingPage "1029" @default.
• W2938369874 abstract "Endothelial–mesenchymal transition (End MT ) has emerged as an essential bioprocess responsible for the development of organ fibrosis. We have previously reported that fibroblast growth factor receptor 1 ( FGFR 1) is involved in the anti‐End MT effect of N ‐acetyl‐seryl‐aspartyl‐lysyl‐proline (Ac SDKP ). FGFR 1 is expressed on the cell membrane and performs its biological function through interaction with co‐receptors, including βklotho ( KLB ). However, it remains unknown whether KLB is involved in the anti‐End MT effects of Ac SDKP . Here, we demonstrated that Ac SDKP increased KLB expression in an FGFR 1‐dependent manner and that KLB deficiency induced Ac SDKP ‐resistant End MT via the induction of the mitogen‐activated protein kinase ( MAPK ) pathway. In cultured endothelial cells, Ac SDKP increased KLB protein level in an FGFR 1‐dependent manner through induction of the FGFR 1– KLB complex. KLB suppression by small interfering RNA transfection did not affect FGFR 1 levels and resulted in the induction of End MT . In contrast to the End MT observed under FGFR 1 deficiency, the End MT induced by KLB suppression was not accompanied by the induction of Smad3 phosphorylation; instead, KLB ‐deficient cells exhibited induced activation of the MAPK /extracellular signal‐regulated kinase ( ERK ) kinase ( MEK ) and ERK pathways. Treatment with the specific MEK inhibitor U0126 diminished KLB deficiency‐induced End MT . Consistent with this finding, Ac SDKP did not suppress either End MT or MEK / ERK activation induced by KLB deficiency. Application of either FGF 19 or FGF 21 synergistically augmented the anti‐End MT effects of Ac SDKP . Taken together, these results indicate that endogenous peptide Ac SDKP exerts its activity through induction of the FGFR 1– KLB complex in vascular endothelial cells." @default.
• W2938369874 created "2019-04-25" @default.
• W2938369874 creator A5060055639 @default.
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• W2938369874 date "2019-04-22" @default.
• W2938369874 modified "2023-10-10" @default.
• W2938369874 title "βklotho is essential for the anti‐endothelial mesenchymal transition effects of <i>N</i> ‐acetyl‐seryl‐aspartyl‐lysyl‐proline" @default.
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• W2938369874 doi "https://doi.org/10.1002/2211-5463.12638" @default.
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• W2938369874 hasPublicationYear "2019" @default.
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