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https://www.readbyqxmd.com/read/29332143/conjunction-of-g-quadruplex-and-stem-loop-in-the-5-untranslated-region-of-mouse-hepatocyte-nuclear-factor-4-alpha1-mediates-strong-inhibition-of-protein-expression
#1
Shangdong Guo, Hong Lu
Hepatocyte nuclear factor 4-alpha (HNF4α) is a well-established master regulator of liver development and function. Restoration of HNF4α can treat multiple liver disorders and liver cancers. To date, HNF4α is still "undruggable" due to lack of known activating ligands. Thus, understanding the regulatory mechanism of HNF4α expression may help develop an alternative approach to modulate HNF4α protein levels. G-quadruplexes (G4) are non-canonical stable secondary structures discovered mostly in the promoters of oncogenes...
January 13, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29330688/hepatocyte-nuclear-factors-as-possible-c-reactive-protein-transcriptional-inducer-in-the-liver-and-white-adipose-tissue-of-rats-with-experimental-chronic-renal-failure
#2
Elzbieta Sucajtys-Szulc, Alicja Debska-Slizien, Boleslaw Rutkowski, Ryszard Milczarek, Iwona Pelikant-Malecka, Tomasz Sledzinski, Julian Swierczynski, Marek Szolkiewicz
Inflammation related to chronic kidney disease (CKD) is an important clinical problem. We recently determined that hepatocyte nuclear factor 1α (HNF1α) was upregulated in the livers of chronic renal failure (CRF) rats-experimental model of CKD. Considering that the promoter region of gene encoding C-reactive protein (CRP) contains binding sites for HNF1α and that the loss-of-function mutation in the Hnfs1α leads to significant reduction in circulating CRP levels, we hypothesized that HNF1α can activate the Crp in CRF rats...
January 12, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29329928/cloning-and-characterization-of-%C3%A2-6-%C3%A2-5-fatty-acyl-desaturase-fad-gene-promoter-in-the-marine-teleost-siganus-canaliculatus
#3
Yewei Dong, Jianhong Zhao, Junliang Chen, Shuqi Wang, Yang Liu, Qinghao Zhang, Cuihong You, Óscar Monroig, Douglas R Tocher, Yuanyou Li
The rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to have the ability of biosynthesizing long-chain polyunsaturated fatty acids (LC-PUFA) from C18 PUFA precursors, and all genes encoding the key enzymes for LC-PUFA biosynthesis have been cloned and functionally characterized, which provides us a potential model to study the regulatory mechanisms of LC-PUFA biosynthesis in teleosts. As the primary step to clarify such mechanisms, present research focused on promoter analysis of gene encoding ∆6/∆5 fatty acyl desaturase (Fad), a rate-limiting enzyme catalyzing the first step in the conversion of C18 PUFA to LC-PUFA...
January 9, 2018: Gene
https://www.readbyqxmd.com/read/29315687/patterning-of-the-hepato-pancreatobiliary-boundary-by-bmp-reveals-heterogeneity-within-the-murine-liver-bud
#4
Amrita Palaria, Jesse R Angelo, Taylor Guertin, Jesse Mager, Kimberly D Tremblay
During development, the endoderm initiates organ-restricted gene expression patterns in a spatiotemporally controlled manner. This process, termed induction, requires signals from adjacent mesodermal derivatives. Fibroblast Growth Factor (FGF) and Bone Morphogenetic Protein (BMP) emanating from the cardiac mesoderm and the septum transversum mesenchyme (STM), respectively, are believed to be simultaneously and uniformly required to directly induce hepatic gene expression from the murine endoderm. Using small molecule inhibitors of BMP signals during liver bud induction in the developing mouse embryo, we find that BMP signaling is not uniformly required to induce hepatic gene expression...
January 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29234104/conjunction-of-potential-g-quadruplex-and-adjacent-cis-elements-in-the-5-utr-of-hepatocyte-nuclear-factor-4-alpha-strongly-inhibit-protein-expression
#5
Shangdong Guo, Hong Lu
Hepatocyte nuclear factor 4-alpha (HNF4α) is a well established master regulator of liver development and function. We identified the in vitro presence of a stable secondary structure, G-quadruplex (G4) in the 5' UTR of P1-HNF4A, the predominant HNF4α isoform(s) in adult liver. Our data suggest that the cooperation of G4 and the adjacent putative protein-binding sites within the 5' UTR was necessary and sufficient to mediate a strong translational repression. This was supported by analysis of deleted/mutated 5'UTRs and two native regulatory single-nucleotide polymorphisms in the 5'UTR...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29215608/h19-lncrna-alters-methylation-and-expression-of-hnf4%C3%AE-in-the-liver-of-metformin-exposed-fetuses
#6
Jie Deng, Martin Mueller, Tingting Geng, Yuanyuan Shen, Ya Liu, Peng Hou, Ramanaiah Ramillapalli, Hugh S Taylor, Michael Paidas, Yingqun Huang
Metformin is the most widely used anti-diabetic medication worldwide. However, human and animal studies suggest that prenatal metformin exposure may increase the risk of metabolic disorders in adult offspring, yet the underpinning mechanism remains unclear. Here we report that metformin-exposed mouse fetuses exhibit elevated expression of the H19 long noncoding RNA, which induces hypomethylation and increased expression of hepatocyte nuclear factor 4α (HNF4α). As a transcription factor essential for morphological and functional differentiation of hepatocytes, HNF4α also has an indispensable role in the regulation of expression of gluconeogenic genes...
December 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29175243/the-molecular-functions-of-hepatocyte-nuclear-factors-in-and-beyond-the-liver
#7
REVIEW
Hwee Hui Lau, Natasha Hui Jin Ng, Larry Sai Weng Loo, Joanita Jasmen, Adrian Kee Keong Teo
The hepatocyte nuclear factors (HNFs) namely HNF1α/β, HNF3α/β/γ, HNF4α/γ and HNF6 are expressed in a variety of tissues/organs such as the liver, pancreas and kidney, in a spatial and temporal manner to regulate embryonic development and subsequently the development of multiple tissues during adulthood. Though the HNFs were initially individually identified due to their roles in the liver, numerous studies have now revealed that the HNFs cross-regulate one another and exhibit synergistic relationships in the regulation of tissue development and function...
November 23, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29150932/high-fat-diet-induced-oxidative-stress-blocks-hepatocyte-nuclear-factor-4%C3%AE-and-leads-to-hepatic-steatosis-in-mice
#8
Dongsheng Yu, Gang Chen, Minglin Pan, Jia Zhang, Wenping He, Yang Liu, Xue Nian, Liang Sheng, Bin Xu
Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease with manifestation of over-accumulation of fat in liver. Increasing evidences indicate that NAFLD may be in part caused by malfunction of very low density lipoprotein (VLDL) secretion. Hepatocyte nuclear factor 4α (HNF4α), a nuclear receptor protein, plays an important role in sustain hepatic lipid homeostasis via transcriptional regulation of genes involved in secretion of VLDL, such as apolipoprotein B (ApoB). However, the exact functional change of HNF4α in NAFLD remains to be elucidated...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29129613/pgc-1%C3%AE-functions-as-a-co-suppressor-of-xbp1s-to-regulate-glucose-metabolism
#9
Jaemin Lee, Mario Andrés Salazar Hernández, Thomas Auen, Patrick Mucka, Justin Lee, Umut Ozcan
OBJECTIVE: Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) promotes hepatic gluconeogenesis by activating HNF4α and FoxO1. PGC-1α expression in the liver is highly elevated in obese and diabetic conditions, leading to increased hepatic glucose production. We previously showed that the spliced form of X-box binding protein 1 (XBP1s) suppresses FoxO1 activity and hepatic gluconeogenesis. The shared role of PGC-1α and XBP1s in regulating FoxO1 activity and gluconeogenesis led us to investigate the probable interaction between PGC-1α and XBP1s and its role in glucose metabolism...
October 28, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29091211/influence-of-abcb11-and-hnf4%C3%AE-genes-on-daclatasvir-plasma-concentration-preliminary-pharmacogenetic-data-from-the-kineti-c-study
#10
Jessica Cusato, Amedeo De Nicolò, Lucio Boglione, Fabio Favata, Alessandra Ariaudo, Simone Mornese Pinna, Federica Guido, Valeria Avataneo, Chiara Carcieri, Giuseppe Cariti, Giovanni Di Perri, Antonio D'Avolio
Background: Daclatasvir is an inhibitor of HCV non-structural 5A protein and is a P-glycoprotein substrate. Pharmacogenetics has had a great impact on previous anti-HCV therapies, particularly considering the association of IL-28B polymorphisms with dual therapy outcome. Objectives: We investigated the association between daclatasvir plasma concentrations at 2 weeks and 1 month of therapy and genetic variants (SNPs) in genes encoding transporters and nuclear factors (ABCB1, ABCB11 and HNF4α)...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29072691/phosphoprotein-enriched-in-diabetes-ped-pea15-promotes-migration-in-hepatocellular-carcinoma-and-confers-resistance-to-sorafenib
#11
Cristina Quintavalle, Sravanth Kumar Hindupur, Luca Quagliata, Pierlorenzo Pallante, Cecilia Nigro, Gerolama Condorelli, Jesper Bøje Andersen, Katrin Elisabeth Tagscherer, Wilfried Roth, Francesco Beguinot, Markus Hermann Heim, Charlotte Kiu Yan Ng, Salvatore Piscuoglio, Matthias Sebastian Matter
Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related death with limited treatment options and frequent resistance to sorafenib, the only drug currently approved for first-line therapy. Therefore, better understanding of HCC tumor biology and its resistance to treatment is urgently needed. Here, we analyzed the role of phosphoprotein enriched in diabetes (PED) in HCC. PED has been shown to regulate cell proliferation, apoptosis and migration in several types of cancer. However, its function in HCC has not been addressed yet...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29051787/increased-expression-of-hepatocyte-nuclear-factor-4-alpha-transcribed-by-promoter-2-indicates-a-poor-prognosis-in-hepatocellular-carcinoma
#12
Shao-Hang Cai, Shi-Xun Lu, Li-Li Liu, Chris Zhiyi Zhang, Jing-Ping Yun
BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. METHODS: A total of 615 HCC specimens were obtained to construct tissue microarrays and perform immunohistochemistry...
October 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29030272/impact-of-fasting-followed-by-short-term-exposure-to-interleukin-6-on-cytochrome-p450-mrna-in-mice
#13
Martin Krøyer Rasmussen, Lærke Bertholdt, Anders Gudiksen, Henriette Pilegaard, Jakob G Knudsen
The gene expression of the cytochrome P450 (CYP) enzyme family is regulated by numerous factors. Fasting has been shown to induce increased hepatic CYP mRNA in both humans and animals. However, the coordinated regulation of CYP, CYP-regulating transcription factors, and transcriptional co-factors in the liver linking energy metabolism to detoxification has never been investigated. Interleukin-6 (IL-6) has been suggested to be released during fasting and has been shown to regulate CYP expression. The present study investigated the hepatic mRNA content of selected CYP, AhR, CAR, PXR and PPARα in mice fasted for 18h and subsequently exposed to IL-6...
October 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29023917/prmt1-and-jmjd6-dependent-arginine-methylation-regulate-hnf4%C3%AE-expression-and-hepatocyte-proliferation
#14
Jie Zhao, Abby Adams, Ben Roberts, Maura O'Neil, Anusha Vittal, Timothy Schmitt, Sean Kumer, Josiah Cox, Zhuan Li, Steven A Weinman, Irina Tikhanovich
Alcohol is a well-established risk factor for hepatocellular carcinoma, but the mechanisms by which it promotes liver cancer are not well understood. Several studies have shown that cellular protein arginine methylation is inhibited by alcohol. Arginine methylation is controlled by the reciprocal activity of protein arginine methyltransferases, primarily PRMT1, and a demethylase JMJD6. The aim of this study was to explore the role of arginine methylation changes in alcohol pathogenesis. We found that PRMT1 activity is inhibited in livers of mice fed with alcohol compared to pair-fed mice...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28981086/engineered-fibroblast-growth-factor-19-protects-from-acetaminophen-induced-liver-injury-and-stimulates-aged-liver-regeneration-in-mice
#15
Gloria Alvarez-Sola, Iker Uriarte, Maria U Latasa, Maddalen Jimenez, Marina Barcena-Varela, Eva Santamaría, Raquel Urtasun, Carlos Rodriguez-Ortigosa, Jesús Prieto, Fernando J Corrales, Anna Baulies, Carmen García-Ruiz, Jose C Fernandez-Checa, Pedro Berraondo, Maite G Fernandez-Barrena, Carmen Berasain, Matías A Avila
The liver displays a remarkable regenerative capacity triggered upon tissue injury or resection. However, liver regeneration can be overwhelmed by excessive parenchymal destruction or diminished by pre-existing conditions hampering repair. Fibroblast growth factor 19 (FGF19, rodent FGF15) is an enterokine that regulates liver bile acid and lipid metabolism, and stimulates hepatocellular protein synthesis and proliferation. FGF19/15 is also important for liver regeneration after partial hepatectomy (PH). Therefore recombinant FGF19 would be an ideal molecule to stimulate liver regeneration, but its applicability may be curtailed by its short half-life...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28963035/mirna-122-protects-mice-and-human-hepatocytes-from-acetaminophen-toxicity-by-regulating-cytochrome-p450-family-2-subfamily-a-member-2-and-e-member-1-expression
#16
Vivek Chowdhary, Kun-Yu Teng, Sharda Thakral, Bo Zhang, Cho-Hao Lin, Nissar Wani, Lei Bruschweiler-Li, Xiaoli Zhang, Laura James, Dakai Yang, Norman Junge, Rafael Brüschweiler, William M Lee, Kalpana Ghoshal
Acetaminophen toxicity is a leading cause of acute liver failure (ALF). We found that miRNA-122 (miR-122) is down-regulated in liver biopsy specimens of patients with ALF and in acetaminophen-treated mice. A marked decrease in the primary miR-122 expression occurs in mice on acetaminophen overdose because of suppression of its key transactivators, hepatocyte nuclear factor (HNF)-4α and HNF6. More importantly, the mortality rates of male and female liver-specific miR-122 knockout (LKO) mice were significantly higher than control mice when injected i...
September 28, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28943765/lactobacillus-acidophilus-ns1-reduces-phosphoenolpyruvate-carboxylase-expression-by-regulating-hnf4%C3%AE-transcriptional-activity
#17
Sung-Soo Park, Garam Yang, Eungseok Kim
Probiotics have been known to reduce high-fat diet (HFD)-induced metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. We recently observed that Lactobacillus acidophilus NS1 (LNS1), distinctly suppresses increase of blood glucose levels and insulin resistance in HFD-fed mice. In the present study, we demonstrated that oral administration of LNS1 with HFD feeding to mice significantly reduces hepatic expression of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in gluconeogenesis which is highly increased by HFD feeding...
2017: Korean Journal for Food Science of Animal Resources
https://www.readbyqxmd.com/read/28943029/generation-of-mouse-and-human-organoid-forming-intestinal-progenitor-cells-by-direct-lineage-reprogramming
#18
Shizuka Miura, Atsushi Suzuki
Intestinal organoids hold great promise as a valuable tool for studying and treating intestinal diseases. The currently available sources of human intestinal organoids, tissue fragments or pluripotent stem cells, involve invasive procedures or complex differentiation protocols, respectively. Here, we show that a set of four transcription factors, Hnf4α, Foxa3, Gata6, and Cdx2, can directly reprogram mouse fibroblasts to acquire the identity of fetal intestine-derived progenitor cells (FIPCs). These induced FIPCs (iFIPCs) form spherical organoids that develop into adult-type budding organoids containing cells with intestinal stem cell properties...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28938650/genomic-variants-link-to-hepatitis-c-racial-disparities
#19
Matthew M Yeh, Sarag Boukhar, Benjamin Roberts, Nairanjana Dasgupta, Sayed S Daoud
Chronic liver diseases are one of the major public health issues in United States, and there are substantial racial disparities in liver cancer-related mortality. We previously identified racially distinct alterations in the expression of transcripts and proteins of hepatitis C (HCV)-induced hepatocellular carcinoma (HCC) between Caucasian (CA) and African American (AA) subgroups. Here, we performed a comparative genome-wide analysis of normal vs. HCV+ (cirrhotic state), and normal adjacent tissues (HCCN) vs...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28935574/taurocholate-induces-biliary-differentiation-of-liver-progenitor-cells-causing-hepatic-stellate-cell-chemotaxis-in-the-ductular-reaction-role-in-pediatric-cystic-fibrosis-liver-disease
#20
Katarzyna N Pozniak, Michael A Pearen, Tamara N Pereira, Cynthia S M Kramer, Priyakshi Kalita-De Croft, Sujeevi K Nawaratna, Manuel A Fernandez-Rojo, Geoffrey N Gobert, Janina E E Tirnitz-Parker, John K Olynyk, Ross W Shepherd, Peter J Lewindon, Grant A Ramm
Cystic fibrosis liver disease (CFLD) in children causes progressive fibrosis leading to biliary cirrhosis; however, its cause(s) and early pathogenesis are unclear. We hypothesized that a bile acid-induced ductular reaction (DR) drives fibrogenesis. The DR was evaluated by cytokeratin-7 immunohistochemistry in liver biopsies, staged for fibrosis, from 60 children with CFLD, and it demonstrated that the DR was significantly correlated with hepatic fibrosis stage and biliary taurocholate levels. To examine the mechanisms involved in DR induction, liver progenitor cells (LPCs) were treated with taurocholate, and key events in DR evolution were assessed: LPC proliferation, LPC biliary differentiation, and hepatic stellate cell (HSC) chemotaxis...
September 19, 2017: American Journal of Pathology
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