scholarly journals miR-1283 Contributes to Endoplasmic Reticulum Stress in the Development of Hypertension Through the Activating Transcription Factor-4 (ATF4)/C/EBP-Homologous Protein (CHOP) Signaling Pathway

2021 ◽  
Vol 27 ◽  
Author(s):  
Weihao Chen ◽  
Tianhao Liu ◽  
Qiuer Liang ◽  
Xudong Chen ◽  
Wencong Tao ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathway ◽  
Homologous Protein ◽  
Activating Transcription Factor 4 ◽  
Activating Transcription Factor ◽  
Transcription Factor 4

FGF19 (fibroblast growth factor 19) as a novel target gene for activating transcription factor 4 in response to endoplasmic reticulum stress

2013 ◽  
Vol 450 (1) ◽  
pp. 221-229 ◽  
Author(s):  
Makoto Shimizu ◽  
Juan Li ◽  
Ryuto Maruyama ◽  
Jun Inoue ◽  
Ryuichiro Sato
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Growth Factor ◽  
Endoplasmic Reticulum Stress ◽  
Fibroblast Growth ◽  
Activating Transcription Factor 4 ◽  
Fgf19 Expression ◽  
Activating Transcription Factor ◽  
Fibroblast Growth Factor 19 ◽  
Transcription Factor 4

FGF19 (fibroblast growth factor 19), expressed in the small intestine, acts as an enterohepatic hormone by mediating inhibitory effects on the bile acid synthetic pathway and regulating carbohydrate and lipid metabolism. In an attempt to identify novel agents other than bile acids that induce increased FGF19 expression, we found that some ER (endoplasmic reticulum) stress inducers were effective. When intestinal epithelial Caco-2 cells were incubated with thapsigargin, marked increases were observed in the mRNA and secreted protein levels of FGF19. This was not associated with the farnesoid X receptor. Reporter gene analyses using the 5′-promoter region of FGF19 revealed that a functional AARE (amino-acid-response element) was localized in this region, and this site was responsible for inducing its transcription through ATF4 (activating transcription factor 4), which is activated in response to ER stress. EMSAs (electrophoretic mobility-shift assays) and ChIP (chromatin immunoprecipitation) assays showed that ATF4 bound to this site and enhanced FGF19 expression. Overexpression of ATF4 in Caco-2 cells induced increased FGF19 mRNA expression, whereas shRNA (short hairpin RNA)-mediated depletion of ATF4 significantly attenuated a thapsigargin-induced increase in FGF19 mRNA.

Endoplasmic reticulum stress induced by hepatitis B virus X protein enhances cyclo-oxygenase 2 expression via activating transcription factor 4

2011 ◽  
Vol 435 (2) ◽  
pp. 431-439 ◽  
Author(s):  
Hyun Kook Cho ◽  
Kyu Jin Cheong ◽  
Hye Young Kim ◽  
JaeHun Cheong
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Critical Role ◽  
Activating Transcription Factor 4 ◽  
B Virus ◽  
Activating Transcription Factor ◽  
Transcription Factor 4 ◽  
Cox2 Expression

Chronic hepatitis B is a disease of the liver that can progress to cirrhosis and liver cancer. The HBx (hepatitis B virus X) protein of hepatitis B virus is a multifunctional regulator that induces ER (endoplasmic reticulum) stress by previously unknown mechanisms. ER stress plays a critical role in inflammatory induction and COX2 (cyclo-oxygenase 2) is an important mediator of this inflammation. In the present study, we demonstrate the molecular mechanisms of HBx on induction of ER stress and COX2 expression. In addition, HBx reduced expression of enzymes which are involved in mitochondrial β-oxidation of fatty acids and the mitochondrial inner membrane potential. The reduction in intracellular ATP levels by HBx induced the unfolded protein response and COX2 expression through the eIF2α (eukaryotic initiation factor 2α)/ATF4 (activating transcription factor 4) pathway. We confirmed that ATF4 binding to the COX2 promoter plays a critical role in HBx-mediated COX2 induction. The results of the present study suggest that HBV infection contributes to induction of hepatic inflammation through dysfunction of cellular organelles including the ER and mitochondria.

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