Fibroblast growth factor 23 (FGF23) is a phosphaturic factor that suppresses both sodium-dependent phosphate transport and production of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] in the proximal tubule. In vitro studies suggest that FGFR3 is the physiologically relevant receptor for FGF23 in the kidney, but this has not been established in vivo. Here, immunohistochemical analysis of the mouse kidn...

AIM To investigate the effects of cyclosporine A (CsA) on thioacetamide (TAA)-induced liver injury. METHODS CsA was co-administrated (7.5 microg/kg body weight per day, i.p.) into rat to investigate the role of CsA on TAA-(200 mg/kg body weight per 3 d for 30 d, i.p.)induced liver injury. RESULTS The data show that TAA caused liver fibrosis in rat after 30 d of treatment. CsA alleviates the...

Endocrine FGF21, FGF19 and co-receptor betaKlotho divert the roles of the canonic fibroblast growth factor receptors (FGFRs) complex from maintaining growth/ proliferation homeostasis to local and systemic metabolic homeostasis. These endocrine factors target adipocytes and hepatocytes leading to alleviation of obesity, fatty liver disease and metabolic abnormalities which are contributing fact...

Hepatocellular carcinoma (HCC), one of the leading causes of cancer-related death, develops from premalignant lesions in chronically damaged livers. Although it is well established that FGF19 acts through the receptor complex FGFR4-β-Klotho (KLB) to regulate bile acid metabolism, FGF19 is also implicated in the development of HCC. In humans, FGF19 is amplified in HCC and its expression is induc...

Fibroblast growth factor (FGF) 19 is a member of the FGF15/19 subfamily of FGFs that includes FGF15/19, FGF21, and FGF23. FGF19 has been shown to have profound effects on liver metabolism and regeneration. FGF19 binds to FGFR4 and its coreceptor β-Klotho to activate intracellular kinases, including Erk1/2. Studies have shown that proinflammatory cytokines such as TNFα impair FGF21 signaling in ...

OBJECTIVE The purpose of this research was to determine how dietary bile acids repress hepatic expression of paraoxonase 1 (PON1). METHODS AND RESULTS C57BL/6 mice and C3H/HeJ mice, having different susceptibilities to atherosclerosis, were fed a chow diet and an atherogenic diet containing taurocholate. Compared with the more atherosclerosis-susceptible C57BL/6 mice, C3H/HeJ mice display res...

The expression of several deletion mutants of fibroblast growth factor receptor 4 (FGFR4) was studied in COS-1 cells. FGFR4-mutants lacking most of the extracellular region did not efficiently reach the plasma membrane but accumulated in the endoplasmic reticulum (ER) and Golgi body. A mutant FGFR4 lacking the kinase domain as well as most of the extracellular region (DeltaExt/R4Tth) had a dist...

Compelling evidence suggests that the epithelial-mesenchymal transition (EMT) correlates with aggressiveness of tumors and poor survival. FGF19 has been shown to be involved in EMT in cholangiocarcinoma and colorectal cancer, however, molecular mechanisms underlying FGF19-induced EMT process in hepatocellular carcinoma (HCC) remain largely unknown. Here, we show the expression of FGF19 is signi...

We have reported that normal human salivary gland-derived epithelial cells exclusively express keratinocyte growth factor receptor (KGFR). In the process of malignant transformation of human salivary gland tumors, KGFR gene expression disappeared concomitantly with the de novo expression of the fibroblast growth factor receptor 1 (FGFR1) and FGFR4 genes. In the present study, we introduced wild...