<i>SREBF2</i>
            -Embedded mir33 Links the Nuclear Bile Acid Receptor FXR to Cholesterol and Lipoprotein Metabolism

Lefèbvre, Philippe; Staels, Bart

doi:10.1161/atvbaha.115.305317

Cited by 5 publications

(5 citation statements)

References 15 publications

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“…The expression of SREBF2 was upregulated in osteoarthritis and played an important role in the pathogenesis of this disease [ 6 , 15 ]. SREBF2 could also directly induce the transcription of transferrin [ 16 ]. In addition, there has been a proven association of ferroptosis with cerebral hemorrhage, traumatic brain injury, carcinogenesis and many degenerative diseases (e.g., Alzheimer’s disease, Parkinson’s disease) [ 17–20 ].…”

Section: Discussionmentioning

confidence: 99%

Stigmasterol alleviates interleukin-1beta-induced chondrocyte injury by down-regulatingsterol regulatory element binding transcription factor 2 to regulateferroptosis

2021

Bioengineered

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Stigmasterol (STM), one of the main active components of Achyranthes bidentata , has been shown to effectively inhibit proinflammatory factors and matrix degradation in chondrocytes. However, the effect of STM on interleukin (IL)-1β-induced chondrocytes and its specific mechanism remain unclear. The purpose of the present study was to explore the effect and mechanism of sterol regulatory element binding transcription factor 2 (SREBF2) on IL-1β induced chondrocytes in the presence of STM. CCK-8 was used to detect the effect of STM on the cell viability of mouse chondrogenic cells (ATDC5). After ATDC5 cells were induced by IL-1β, the expression of SREBF2 in osteoarthritis cells was detected by RT-qPCR. The content of iron ion in the cells was detected by using an iron colorimetric assay kit. After further transfection of a SREBF2 overexpressing vector (Oe-SREBF2) or addition of a ferroptosis inhibitor, the expression levels of inflammation and matrix degradation-related proteins were detected via Western blotting. The levels of oxidative stress in cells were determined by using an ELISA kit. The results revealed that STM had no significant effect on the viability of ATDC5 cells. STM reduced IL-1β-induced ATDC5 cell damage and ferroptosis through SREBF2 and enhanced the inhibitory effect of ferroptosis inhibitors on IL-1β-induced ATDC5 cell injury. The present data suggest that STM attenuated chondrocyte injury induced by IL-1β by regulating ferroptosis via down-regulation of SREBF2, and may have potential as a novel therapeutic method for knee osteoarthritis.

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Section: Discussionmentioning

confidence: 99%

Stigmasterol alleviates interleukin-1beta-induced chondrocyte injury by down-regulatingsterol regulatory element binding transcription factor 2 to regulateferroptosis

2021

Bioengineered

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“…Most of intestinal BA are reabsorbed in the distal part of small intestine and transported back to the liver via enterohepatic circulation ( 14 ). Thus, BSEP transports BA from liver into the bile ducts, ASBT (apical sodium-dependent bile transporter or Slc10a2) and IBABP (ileal bile acid binding protein) facilitate the exit of BA from the intestine into the enterohepatic circulation, while NTCP (Na + -taurocholic acid co-transporting polypeptide or Slc10a1) mediates absorption of BA from blood circulation into the liver ( 15 ). Several genetic mutations of these proteins were identified in humans as being the cause of cholestatic diseases (Table 1 ).…”

Section: Cell and Molecular Aspects Of Liver Physiologymentioning

confidence: 99%

“…SHP is an atypical orphan nuclear receptor, does not have a DNA-binding domain and acts as a repressor by interacting with specific nuclear receptors such as HNF4α (hepatocyte nuclear factor 4-α), LXR (liver X receptor), FTF (fetoprotein transcription factor), to repress transcription of key genes with role in BA biosynthesis (e.g., cytochrome P proteins CYP7A1, CYP8B, CYP27A1), conjugation (VLACSR or very long chain acyl-CoA synthetase related gene; BAT or BA-CoA: amino acid N-acyltransferase) ( 39 ) and transport along the enterohepatic circulation (NTCP) ( 10 , 12 , 40 ). FXR was also found to upregulate genes that mediate bile efflux from the liver to biliary canaliculi, such as BSEP/ABCB11 and MDR3/ABCB4; FXR also stimulates the expression of OSTα and OSTβ (organic solute transporters) in basolateral membranes of hepatocytes and in ileal enterocytes, as well as intestinal expression of IBABP (intestinal bile acid-binding protein), mediating BA efflux from the liver or intestine to the portal vein ( 15 ). Thus, BA function as signaling molecules with specific affinity for FXR, regulating BA homeostasis.…”

Section: Cell and Molecular Aspects Of Liver Physiologymentioning

confidence: 99%

Hypothalamus-Pituitary-Adrenal Dysfunction in Cholestatic Liver Disease

et al. 2018

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The Hypothalamic-Pituitary-Adrenal (HPA) axis has an important role in maintaining the physiological homeostasis in relation to external and internal stimuli. The HPA axis dysfunctions were extensively studied in neuroendocrine disorders such as depression and chronic fatigue syndrome but less so in hepatic cholestasis, cirrhosis or other liver diseases. The HPA axis controls many functions of the liver through neuroendocrine forward signaling pathways as well as negative feedback mechanisms, in health and disease. This review describes cell and molecular mechanisms of liver and HPA axis physiology and pathology. Evidence is presented from clinical and experimental model studies, demonstrating that dysfunctions of HPA axis are correlated with liver cholestatic disorders. The functional interactions of HPA axis with the liver and immune system in cases of bacterial and viral infections are also discussed. Proinflammatory cytokines stimulate glucocorticoid (GC) release by adrenals but they also inhibit bile acid (BA) efflux from liver. Chronic hepatic inflammation leads to cholestasis and impaired GC metabolism in the liver, so that HPA axis becomes depressed. Recently discovered interactions of GC with self-oscillating transcription factors that generate circadian rhythms of gene expression in brain and liver, in the context of GC replacement therapies, are also outlined.

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“…Its dietary absorption, synthesis, release, transportation, and storage are all tightly regulated [ 125 ]. Free cholesterol and triglyceride are secreted from the liver to other parts of the body in the form of VLDL with the help of the chaperone protein called microsomal triglyceride transfer protein (MTP) [ 126 ].…”

Section: Cholesterol Metabolismmentioning

confidence: 99%

“…SREBPs, with the basic helix-loop-helix leucine zipper motif, activated under cholesterol limit conditions, are the major regulators of fatty acid and cholesterol homeostasis [ 125 ]. SREBP2 enhances cholesterol uptake and synthesis by activating LDL receptor (LDLR), scavenger receptor B1 (SRB1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA-R), 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMG-CoA-S1), and methylsterol monoxygenase (SC4MOL) and decreases cholesterol effl ux via suppressing ABCA1, ABCG1, ATP-binding cassette transporter G5/G8 (ABCG5/ABCG8), and cholesterol 7-alpha-monooxygenase also known as cytochrome P450 7A1 (CYP7A1).…”

Section: Srebps Lxr Pparα and Signal Transduction Pathwaysmentioning

confidence: 99%

Noncoding RNAs in Regulation of Cancer Metabolic Reprogramming

Yang

Sun

et al. 2016

Advances in Experimental Medicine and Biology

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Since the description of the Warburg effect 90 years ago, metabolic reprogramming has been gradually recognized as a major hallmark of cancer cells. Mounting evidence now indicates that cancer is a kind of metabolic disease, quite distinct from conventional perception. While metabolic alterations in cancer cells have been extensively observed in glucose, lipid, and amino acid metabolisms, its underlying regulatory mechanisms are still poorly understood. Noncoding RNA, also known as the "dark matter in life," functions through various mechanisms at RNA level regulating different biological pathways. The last two decades have witnessed the booming of noncoding RNA study on microRNA (miRNA), long noncoding RNA (lncRNA), circular RNA (circRNA), PIWI-interacting RNA (piRNA), etc. In this chapter, we will discuss the regulatory roles of noncoding RNAs on cancer metabolism.

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SREBF2 -Embedded mir33 Links the Nuclear Bile Acid Receptor FXR to Cholesterol and Lipoprotein Metabolism

Cited by 5 publications

References 15 publications

Stigmasterol alleviates interleukin-1beta-induced chondrocyte injury by down-regulatingsterol regulatory element binding transcription factor 2 to regulateferroptosis

Stigmasterol alleviates interleukin-1beta-induced chondrocyte injury by down-regulatingsterol regulatory element binding transcription factor 2 to regulateferroptosis

Hypothalamus-Pituitary-Adrenal Dysfunction in Cholestatic Liver Disease

Noncoding RNAs in Regulation of Cancer Metabolic Reprogramming

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