ライフサイエンスコーパス: FXR

1 FXR activation in hepatic stellate cells (HSCs) reduces

2 FXR activation induced antioxidative pathways, which was

3 FXR agonists are currently being evaluated as therapeuti

4 FXR agonists reduce lipid accumulation in the liver, hep

5 FXR also regulates postprandial lipid and glucose metabo

6 FXR and MYC were also discovered in our analysis as two

7 FXR and RXRalpha expressions were significantly reduced,

8 FXR and TGR5 are modulators of glucose metabolism, and F

9 FXR deficiency enriched Desulfovibrionaceae, Deferribact

10 FXR deficiency increased the contribution of glutamine a

11 FXR is also essential for maintaining bile acid homeosta

12 FXR KO also had reduced Firmicutes and increased Proteob

13 FXR plays critical roles in other lipid metabolic pathwa

14 FXR proteins drive the assembly of vRCs of Venezuelan eq

15 FXR upregulates Perilipin-1, a direct target gene of FXR

16 FXR was downregulated in all hepatocyte cell lines and p

17 FXR-mediated regulation of MMP7 transcription did not re

18 1, and ileum ASBT and decreased liver IL-10, FXR, CAR, VDR, BSEP, MRP2, MRP3, MRP4 was also observed

19 Mithramycin is a FXR expression and FXR transactivation inhibitor that in

20 exor (LJN452), the most potent non-bile acid FXR agonist currently in clinical investigation.

21 of a novel chemical series of non-bile acid FXR agonists based on a tricyclic dihydrochromenopyrazol

22 novel series of highly potent non-bile acid FXR agonists that introduce a bicyclic nortropine-substi

23 The bile acid-FXR interaction regulates bile acid synthesis, transport

24 stigate the role of raised serum bile acids, FXR and TGR5 in gestational glucose metabolism using mou

25 Elevated bile acids activate FXR, which in turn switches off bile acid synthesis by r

26 onic liver diseases; compounds that activate FXR might promote ammonium clearance in these patients.

27 Obeticholic acid (OCA) was used to activate FXR both in mice and in human hepatocellular carcinoma (

28 ment and characterization of a high-affinity FXR modulator not comprising an acidic residue.

29 er whose expression was down-regulated after FXR activation.

30 and predicted microbiota functions were all FXR-dependent.

31 tified the RNA-binding protein Zfp36l1 as an FXR target gene and determined that gain and loss of fun

32 esoid X receptor (FXR), mice that express an FXR transgene specifically in the intestine, and ABCG8-k

33 EEV replication can be also switched from an FXR-dependent to a chikungunya virus-specific, G3BP-depe

34 We identified an FXR-responsive element on the Tgr5 gene promoter.

35 Feeding or treatment with an FXR agonist induced Abcg5/8 and Scarb1 expression in WT,

36 Mithramycin is a FXR expression and FXR transactivation inhibitor that inhibits bile flow an

37 a nuclear receptor cascade involving FXR and FXR-induced small heterodimer partner (SHP) regulates ex

38 letions of the binding sites of the G3BP and FXR protein families in the nsP3 HVD of EEEV make the vi

39 oach by combining SUMOylation inhibitors and FXR agonists for liver fibrosis.

40 In both hepatic FXR-knockout and FXR-knockdown mice, reconstitution of FXR expression up-

41 uman and murine colon cancer cell lines, and FXR transgenic mice, here we identified an additional, p

42 NA expression of HSCs activation markers and FXR engagement were evaluated at 24, 96 and 144 hours.

43 R5 are modulators of glucose metabolism, and FXR activity is reduced in normal pregnancy, and further

44 idence that hepatic targets of PPARalpha and FXR are dysregulated in chronic undernutrition.

45 We conclude that PPARalpha and FXR function coordinately to integrate liver energy bala

46 anding of the binding of CD2AP, SH3KBP1, and FXR protein family members to VEEV HVD uncovers importan

47 Wild-type and FXR KO mice were on a control (CD) or Western diet (WD)

48 and islet cells from C57BL/6N wild-type and FXR-knockout (KO) mice.

49 partial FXR agonistic activity in vitro and FXR-dependent gene modulation in vivo.

50 ydrate, were used to feed wild type (WT) and FXR knockout (KO) mice followed by phenotyping character

51 come by intestinal bile acids functioning as FXR agonists.

52 EGFR expression is indirectly induced by BA-FXR through activation of suppressor of cytokine signali

53 tructurally refined to a potent and balanced FXR/PPARdelta activator in a computer-aided fashion.

54 Both FXR and SHP inhibit hepatic autophagy interdependently,

55 Activation of both FXR and TGR5 may therefore represent an effective therap

56 n mouse liver cells, 89% of sites that bound FXR were bound by only FXRalpha2 or FXRalpha4, via direc

57 nstrate that normal inhibition of miR-802 by FXR-SHP is defective in obesity, resulting in increased

58 expression, which was markedly attenuated by FXR antagonist.

59 ilicity of the bile salt pool, controlled by FXR and FGF15/19, is an important determinant of cholest

60 FGF15 is induced by FXR in ileal enterocytes in response to increased amount

61 ctly suppressed by PPARalpha, but induced by FXR.

62 fy the renal signaling pathways regulated by FXR and TGR5, which may be promising targets for the tre

63 Most metabolic effects regulated by FXR in mouse and human liver cells are regulated by the

64 lts suggest that WD increases cancer risk by FXR inactivation, leading to BA deregulation and increas

65 ch is induced by PPARalpha but suppressed by FXR.

66 amily 1 group H member 4 (NR1H4, also called FXR) is a ligand-activated transcription factor that, up

67 In LX-2 cells, FXR activation increased peroxisome proliferator-activat

68 which interact with the members of cellular FXR and G3BP protein families, made EEEV cease to be neu

69 de preclinical proof-of-concept for combined FXR and PPAR-alpha/delta agonist-based therapies in NASH

70 Conclusion: FXR and TGR5 play critical roles in protecting the liver

71 sed intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholester

72 ed therapies for NASH, the bile acid-derived FXR agonist obeticholic acid (OCA; 6-ethyl chenodeoxycho

73 We have designed a minimal dual FXR/PPARdelta activator scaffold by rational fusion of p

74 The resulting dual FXR/PPARdelta modulator comprises high selectivity over

75 Here, we studied the effects of the dual FXR and TGR5 agonist INT-767 on hepatic bile acid synthe

76 diabetic DBA/2J and db/db mice with the dual FXR/TGR5 agonist INT-767 improved proteinuria and preven

77 agonist obeticholic acid (OCA) and the dual FXR/TGR5 agonist INT-767 in a well-established co-cultur

78 A lack of interaction with either FXRs or G3BPs does not affect vRC formation; however, re

79 sed BAs in Fgf15(-/-) mice leads to enhanced FXR activation in HSCs, subsequently reducing fibrogenes

80 o OCA and other FXR agonists due to enhanced FXR SUMOylation.

81 r1h4, which encodes the transcription factor FXR that is required for maximal urinary concentration.

82 esponses according to food intake, featuring FXR as a T cell-intrinsic sensor.

83 T mice harboring simple steatosis and CD-fed FXR KO mice, in which the steatosis had a potential to d

84 In addition, both CD- and WD-fed FXR KO male mice, which had hepatic lymphocyte and neutr

85 cteria and Bacteroidetes persisted in WD-fed FXR KO mice even after Abx treatment.

86 Male WD-fed FXR KO mice had the most severe steatohepatitis.

87 Our data revealed that male WD-fed FXR KO mice had the most severe steatosis and highest he

88 B could reduce hepatic lymphocytes in WD-fed FXR KO mice.

89 s and lymphocytes in CD-fed, but not WD-fed, FXR KO mice.

90 Consistent with this finding, FXR overexpression and a dominant-negative FXR mutation

91 ine kinase Src was shown to be important for FXR function in BA homeostasis.

92 This unexpected role for FXR in coordinating intestinal self-renewal with BA leve

93 n additional, potentially important role for FXR.

94 11beta position affords high selectivity for FXR.

95 We found FXR to bind to regulatory sites of genes encoding these

96 Liver tissues from FXR-knockout mice had reduced expression of urea cycle p

97 Furthermore, FXR activation induced expression of FXR target genes, i

98 effects of bile acids and on the other hand, FXR determines the level of impairment of islet function

99 In both hepatic FXR-knockout and FXR-knockdown mice, reconstitution of F

100 We conclude that phosphorylation of hepatic FXR by FGF15/19-induced Src maintains cholesterol homeos

101 chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis.

102 h luciferase reporters using mouse and human FXR isoforms.

103 on daf-12 (a functional homolog of the human FXR) with upregulation of ech-1.1 (a homolog of enoyl-Co

104 xylase mRNA levels were induced, while ileum FXR target genes were suppressed in DKO mice compared to

105 These previous observations implicate FXR as a tumor suppressor, but the underlying molecular

106 tinal self-renewal with BA levels implicates FXR as a potential therapeutic target for CRC.

107 blunted by substitution of Phe for Tyr-67 in FXR.

108 Hepatic miR-802 levels are increased in FXR-knockout (KO) or SHP-KO mice and are decreased by ac

109 crobiota that affect hepatic inflammation in FXR knockout (KO) mice.

110 ulation, leading to considerable interest in FXR as a therapeutic target for the treatment of cholest

111 rease in insulin release was also present in FXR-KO mice.

112 The variability in FXR expression level/activity, for instance in individua

113 HSCs from Fgf15(-/-) mice showed increased FXR activity and reduced expression of profibrotic media

114 ouse liver organoids that express individual FXR isoforms using chromatin immunoprecipitation, follow

115 ed the FXR ligand obeticholic acid to induce FXR activity in organoids, cell lines, and mice.

116 ed chenodeoxycholic acid- and GW4046-induced FXR-galactose-induced gene 4 luciferase reporter activit

117 acid pool, liver fibrosis, and inflammation; FXR and TGR5 DKO mice may be a model for liver fibrosis.

118 we found TICE to be regulated by intestinal FXR via induction of its target gene Fgf15 (FGF19 in rat

119 CA supplementation induced intestinal FXR signaling, which was not abrogated by pregnancy, wit

120 nversely, selective activation of intestinal FXR can restrict abnormal Lgr5(+) cell growth and curtai

121 The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene exp

122 ancy were associated with reduced intestinal FXR signaling, with lower FGF19/15 and resultant increas

123 (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepa

124 whether a nuclear receptor cascade involving FXR and FXR-induced small heterodimer partner (SHP) regu

125 These findings identify that NF-kappaB/FXR-dependent impaired bile secretion promotes intrahepa

126 d by decreased mRNA expression of well-known FXR target genes, hepatic small heterodimer partner, and

127 h transcriptional activation of lipogenesis, FXR-RXR, PPAR-alpha mediated lipid oxidation and oxidati

128 In addition, liver FXR-knockout mice had reduced hepatic expression of enzy

129 In liver FXR-knockout mice on a high-protein diet, the plasma con

130 th liver-specific disruption of Nr1h4 (liver FXR-knockout mice) were re-fed with a high-protein diet

131 reducing ileal bile acid uptake and lowering FXR induction in enterocytes.

132 In livers of mice, FXR regulates amino acid catabolism and detoxification o

133 f FXR was reduced by atorvastatin in a mouse FXR reporter assay.

134 MMP7 transcription by binding to a negative FXR-responsive element in the 5' MMP7 promoter, an event

135 , FXR overexpression and a dominant-negative FXR mutation reduced and augmented, respectively, MMP7 e

136 nd in rodent models of intestinal neoplasia, FXR knockout increases the size and number of colon tumo

137 er, we used mice with a disruption of Nr1h4 (FXR-knockout mice) and compared them with floxed control

138 ulatory activities of the hepatic TR, NR1H4 (FXR; farnesoid X receptor), as our model system to tackl

139 promote viral replication in the absence of FXR-HVD interactions albeit less efficiently.

140 In obese mice, activation of FXR by obeticholic acid treatment reduced miR-802 levels

141 P-KO mice and are decreased by activation of FXR in a SHP-dependent manner.

142 mediated through increased BA activation of FXR in HSCs.

143 vel mechanism in which INT-767 activation of FXR induces Tgr5 gene expression and increases Ca(2+) le

144 Activation of FXR inhibits bile acid synthesis and increases bile acid

145 Activation of FXR suppressed kidney fibrosis and downregulated Smad3 e

146 e and primary rat hepatocytes, activation of FXR with obeticholic acid increased expression of protei

147 Nuclear activity of FXR was reduced by atorvastatin in a mouse FXR reporter

148 JN452), a novel and highly potent agonist of FXR.

149 We collected data on the binding of FXR in mouse liver and the expression levels of FXR isof

150 We determined genome-wide binding of FXR isoforms in mouse liver organoids that express indiv

151 Deletion of FXR in T cells prevented starvation-induced loss of lymp

152 This study also revealed a dysregulation of FXR signaling in the liver and intestine of NAFLD mice t

153 im of this study was to assess the effect of FXR activation on gene expression and phenotype of the l

154 lta-mediated activity and hepatic effects of FXR activation appear as a promising multitarget approac

155 TGR5 that demonstrated beneficial effects of FXR and TGR5 activation in the kidney, we reasoned that

156 verse relationship between the expression of FXR and matrix metalloproteinase-7 (MMP7), a collagenase

157 and caloric restriction on the expression of FXR and TGR5 in the kidney.

158 nalysis revealed downregulated expression of FXR in HNF-1beta mutant kidneys.

159 Down-regulated expression of FXR plays an important role in some malignancies such as

160 ermore, FXR activation induced expression of FXR target genes, including fibroblast growth factor 15,

161 olipoprotein E-deficient mice, expression of FXR, but not Y67F-FXR, ameliorated atherosclerosis, wher

162 tion by BAs, the gene-regulatory function of FXR is also modulated by hormone or nutrient signaling-i

163 gulates Perilipin-1, a direct target gene of FXR, to stabilize lipid droplets and thereby prevent HSC

164 abolism may underlie the hepatoprotective of FXR activation during VPA treatment.

165 dent PD models by measuring the induction of FXR target genes in various tissues.

166 IRT1 depletion correlated with inhibition of FXR, whereas modulation of SIRT1 by NorUDCA associated w

167 ome mice with intestine-specific knockout of FXR were given daily injections of fibroblast growth fac

168 in mouse liver and the expression levels of FXR isoforms and gene targets in human liver tissue and

169 ion may be a novel antifibrotic mechanism of FXR agonism, and EDP-305 could be used to treat renal fi

170 more, FGF19 treatment increased occupancy of FXR at Abcg5/8 and Scarb1, expression of these genes, an

171 ut and FXR-knockdown mice, reconstitution of FXR expression up-regulated cholesterol transport genes

172 Here, we investigated the protective role of FXR against kidney damage induced by obesity in mice tha

173 epatocytes were used to validate the role of FXR in amino acid catabolism by gene expression and meta

174 A role of FXR in drug-induced liver injury has also been hypothesi

175 To study the role of FXR in mouse liver, we used mice with a disruption of Nr

176 The role of FXR in regulation of bile acid synthesis and hepatic met

177 However, the role of FXR in renal fibrosis remains to be established.

178 Extended stimulation of FXR by the synthetic agonist GW4064, which is suggested

179 hich is suggested to induce translocation of FXR from the cytosol into the nucleus, increased the inh

180 their roles are not as critical as those of FXRs and G3BPs.

181 nist lead compound exhibited weak agonism on FXR and PPARdelta and was structurally refined to a pote

182 HSCs show limited response to OCA and other FXR agonists due to enhanced FXR SUMOylation.

183 oncept, we developed agents exerting partial FXR agonism and sEH inhibitory activity.

184 nidufexor (LMB763), a compound with partial FXR agonistic activity in vitro and FXR-dependent gene m

185 onsistent with Src's role in phosphorylating FXR, Src knockdown impaired cholesterol regulation in mi

186 To date, potent FXR agonists share a negatively ionizable function that

187 Although not a prerequisite, FXR seems to influence the degree of damage caused by at

188 reduced activity of the nuclear BA receptor FXR.

189 endogenous ligands for the nuclear receptor FXR.

190 In particular, farnesoid X receptor (FXR) activation that revealed antisteatotic and antifibr

191 Farnesoid X receptor (FXR) agonists are emerging as important potential therap

192 SGLT2) inhibitors, and farnesoid X receptor (FXR) agonists, with further novel treatments on the hori

193 otent agonists for the farnesoid X receptor (FXR) and dual peroxisome proliferator-activated receptor

194 nsing nuclear receptor farnesoid X receptor (FXR) and epigenetically up-regulates FXR targets importa

195 clear hormone receptor farnesoid X receptor (FXR) and G protein-coupled membrane receptor TGR5 that d

196 transcription factors farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPA

197 Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are important r

198 amycin not only alters farnesoid X receptor (FXR) and small heterodimer partner gene expression but a

199 clear hormone receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5.

200 ted receptors, nuclear farnesoid X receptor (FXR) and the membrane Takeda G-protein receptor 5 (TGR5)

201 mation via the nuclear farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5).

202 ated receptors nuclear farnesoid X receptor (FXR) and transmembrane G-protein-coupled membrane recept

203 dent of the microbiome-farnesoid X receptor (FXR) axis.

204 is induced by diet and farnesoid X receptor (FXR) deficiency in both genders.

205 antagonize intestinal farnesoid X receptor (FXR) function, including tauro-beta-muricholic acid (T-b

206 Activation of the farnesoid X receptor (FXR) has indicated a therapeutic potential for this nucl

207 The function of the farnesoid X receptor (FXR) in DKO mice was lower, revealed by decreased mRNA e

208 Farnesoid X receptor (FXR) induces fibroblast growth factor 15 (FGF15; human o

209 The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of

210 The farnesoid X receptor (FXR) is a nuclear receptor that acts as a master regulat

211 Farnesoid X receptor (FXR) is a nuclear receptor that has emerged as a key reg

212 Farnesoid X receptor (FXR) is a promising target for nonalcoholic steatohepati

213 ular bile acid sensor, farnesoid X receptor (FXR) participates in regulation of bile acid, lipid and

214 ear bile acid receptor farnesoid X receptor (FXR) protects against hepatic inflammation and injury, w

215 crease of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid c

216 tive activation of the farnesoid X receptor (FXR) reduces PPARgamma hepatic expression and induces he

217 of SCD mice inhibited farnesoid X receptor (FXR) signaling and its downstream targets, leading to lo

218 Farnesoid X receptor (FXR), a key regulator of hepatic energy metabolism, has

219 s mediated through the farnesoid X receptor (FXR), as demonstrated in Fxr(-/-) mice, and involved EGF

220 ecific knockout of the farnesoid X receptor (FXR), mice that express an FXR transgene specifically in

221 Farnesoid X receptor (FXR), or NR1H4, protects the liver from insults of vario

222 egulated expression of Farnesoid X receptor (FXR), small heterodimer partner (SHP) and bile salt expo

223 led to the activity of farnesoid X receptor (FXR)-dependent signaling pathways in beta cells.

224 Terminal ileal farnesoid X receptor (FXR)-mediated gene expression and apical sodium bile aci

225 ated activation of the farnesoid X receptor (FXR).

226 ncer also have reduced farnesoid X receptor (FXR).

227 e the nuclear receptor farnesoid X receptor (FXR).

228 lear hormone receptor, farnesoid X receptor (FXR).

229 n the nuclear receptor Farnesoid X Receptor (FXR).

230 ulin secretion via the farnesoid X receptor (FXR).

231 tabolism by modulating farnesoid X receptor (FXR); we here investigate its role in cholestatic liver

232 (encoded by NR1C1) and farnesoid X receptor (FXR, encoded by NR1H4) are activated in the liver in the

233 (BA) nuclear receptor, farnesoid X receptor (FXR/NR1H4), maintains metabolic homeostasis by transcrip

234 rrogate for intestinal farnesoid X receptor [FXR] activity), patatin-like phospholipase domain contai

235 p H member 4 (NR1H4 or farnesoid X receptor [FXR]) regulates bile acid synthesis, transport, and cata

236 e response via bile acid-activated receptors FXR and TGR5 represents a new potential treatment strate

237 is a known agonist of farnesoid X receptors (FXR), which are involved in cholesterol homeostasis.

238 ose that raised serum bile acids and reduced FXR and TGR5 activity contribute to the altered glucose

239 COL1A1 expression, but significantly reduced FXR and induced SHP expression, as expected.

240 ceptor (FXR) and epigenetically up-regulates FXR targets important for the regulation of BA levels, s

241 ontain one or more of the Fragile X related (FXR) proteins (FMRP, FXR2P, and FXR1P) along with mRNA a

242 tingly, in long-lived Ames dwarf mice, renal FXR and TGR5 expression levels were also increased.

243 SUMOylation inhibitors rescue FXR signaling and thereby increasing the efficacy of OCA

244 Blocking NF-kappaB activation rescued FXR signaling and partially ameliorated liver injury and

245 of SIRT1 by NorUDCA associated with restored FXR signaling.

246 Together, the presented data revealed FXR-dependent concomitant relationships between gut micr

247 ngenuity Pathways Analysis, such as LXR/RXR, FXR/RXR activation (- log[P-value] = 30-31) and atherosc

248 ined the individual effects of the selective FXR agonist obeticholic acid (OCA) and the TGR5 agonist

249 efficiently utilizes both the VEEV-specific FXR protein family and the Old World alphavirus-specific

250 In summary, FXR activation maintains endogenous glutathione homeosta

251 outcomes of patients given drugs that target FXR.

252 Therefore, we conclude that FXR may promote the proliferation of tumor cells and the

253 We found that FXR and TGR5 expression levels are decreased in the agin

254 In summary, our results indicate that FXR and TGR5 may play an important role in modulation of

255 e retinoid X receptor (RXR), indicating that FXR represses MMP7 expression independently of RXR.

256 We noted that FXR gene ablation increases MMP7 expression.

257 5 activation in the kidney, we reasoned that FXR and TGR5 could be excellent candidates.

258 Luciferase reporter assay revealed that FXR activation inhibited the transcriptional activity of

259 Here, we show that FXR activation triggers a rapid posttranscriptional mech

260 We have shown that FXR and TGR5 have renoprotective roles in diabetes- and

261 These results suggested that FXR may serve as an important negative regulator for man

262 Last, we uncovered that FXR suppresses MMP7 transcription by binding to a negati

263 The FXR agonist OCA and the TGR5 agonist INT-777 modulated d

264 We administered the FXR/TGR5 dual agonist INT-767 to DBA/2J mice with strept

265 r for manipulating Smad3 expression, and the FXR/Smad3 pathway may be a novel target for the treatmen

266 tly represented HVD-binding proteins are the FXR and G3BP family members.

267 ucose and lipid metabolism more than did the FXR-selective obeticholic acid and TGR5-selective INT-77

268 Transcript variants encode the FXR isoforms alpha 1, alpha 2, alpha 3, and alpha 4, whi

269 organoids and HepG2 cells that expressed the FXR isoforms using chromatin immunoprecipitation, quanti

270 These findings identify the FXR-MMP7 axis as a potential therapeutic target for mana

271 Here, we investigate the effects of the FXR agonist EDP-305 in a mouse model of tubulointerstiti

272 ein, we assessed in vitro the effects of the FXR agonist obeticholic acid (OCA) and the dual FXR/TGR5

273 ein interacts with all of the members of the FXR and G3BP protein families, and only a lack of intera

274 VEEV nsP3 interacts with the members of the FXR family of cellular proteins and also binds the Src h

275 ing loss-of-function genetic variants of the FXR gene, could contribute to valproic acid pharmacokine

276 Here we performed a systematic survey of the FXR protein composition and mRNA association of FXGs in

277 We used the FXR ligand obeticholic acid to induce FXR activity in or

278 tionally licensed add-on therapy is with the FXR (NR1H4) agonist, obeticholic acid.

279 Mice were gavaged with the FXR agonist obeticholic acid or vehicle for 11 days.

280 control diet or a diet supplemented with the FXR agonist PX20606, with or without the cholesterol abs

281 tment of 22-month-old C57BL/6J mice with the FXR-TGR5 dual agonist INT-767 induced caloric restrictio

282 c risk and are reported to interact with the FXR.

283 types that can be categorized based on their FXR protein complement.

284 This FXR-SHP-miR-802 pathway may present novel targets for tr

285 Here, we examined the role of this FXR phosphorylation in cholesterol regulation.

286 ssion but also inhibits bile acid binding to FXR, resulting in deregulation of cellular bile homeosta

287 ile acids enabling secondary modification to FXR agonists, enhancing enterohepatic feedback via FGF19

288 milar BA profile, and maintained response to FXR activation.

289 However, response to FXR synthetic ligands was maintained in DKO mice as trea

290 Clinical results have validated FXR as therapeutic target in hepatic and metabolic disea

291 Although various FXR agonists have shown anti-fibrotic effects in diverse

292 uate these functions and investigate whether FXR regulates amino acid metabolism.

293 However, it remains unclear whether FXR plays direct anti-fibrotic effect in renal fibrosis

294 epatic autophagy interdependently, but while FXR acts early, SHP acts relatively late after feeding,

295 tivation induces fatty acid oxidation, while FXR controls bile acid homeostasis, but both nuclear rec

296 3) treatment of a human HSC line, LX-2, with FXR activators and/or recombinant FGF19 protein.

297 Interactions with FXR family members are mediated by the C-terminal repeat

298 dict responses of patients to treatment with FXR agonists.

299 icient mice, expression of FXR, but not Y67F-FXR, ameliorated atherosclerosis, whereas Src down-regul

300 19-mediated effects were blunted by the Y67F-FXR substitution or Src down-regulation or inhibition.