Abstract:
:The prevalence of non-alcoholic fatty liver disease (NAFLD), a condition characterized by an excessive accumulation of triglycerides (TGs) in hepatocytes, has dramatically increased globally during recent decades. MicroRNAs (miRs) have been suggested to play crucial roles in many complex diseases and lipid metabolism. Our results indicated that miR199a-5p was remarkably upregulated in free fatty acid (FA)-treated hepatocytes. To investigate the role of miR199a-5p in the pathogenesis of fatty liver and the potential mechanism by which miR199a-5p regulates NAFLD, we first transfected two hepatocyte cell lines, HepG2 and AML12 cells, with agomiR199a-5p or antagomiR199a-5p. Our results indicated that miR199a-5p overexpression exacerbated deposition of FA and inhibited ATP levels and mitochondrial DNA (mtDNA) contents. Consistently, suppression of miR199a-5p partially alleviated deposition of FA and increased ATP levels and mtDNA contents. Moreover, miR199a-5p suppressed the expression of mitochondrial FA β-oxidation-related genes through inhibition of caveolin1 (CAV1) and the related peroxisome proliferator-activated receptor alpha (PPARα) pathway. Furthermore, suppression of CAV1 gene expression by CAV1 siRNA inhibited the PPARα signalling pathway. Finally, we examined the expression of miR199a-5p in liver samples derived from mice fed a high-fat diet, db/db mice, ob/ob mice and NAFLD patients, and found that miR199a-5p was upregulated while CAV1 and PPARA were downregulated in these systems, which was strongly indicative of the essential role of miR199a-5p in NAFLD. In summary, miR199a-5p plays a vital role in lipid metabolism, mitochondrial activity and mitochondrial β-oxidation in liver. Upregulated miR199a-5p in hepatocytes may contribute to impaired FA β-oxidation in mitochondria and aberrant lipid deposits, probably via CAV1 and the PPARα pathway.
journal_name
J Mol Endocrinoljournal_title
Journal of molecular endocrinologyauthors
Li B,Zhang Z,Zhang H,Quan K,Lu Y,Cai D,Ning Gdoi
10.1530/JME-14-0127subject
Has Abstractpub_date
2014-12-01 00:00:00pages
393-403issue
3eissn
0952-5041issn
1479-6813pii
JME-14-0127journal_volume
53pub_type
杂志文章abstract::Activins are cytokines of the transforming growth factor beta family, which plays a central role in the determination of cell fate and the regulation of tissue balance. Family members are composed of two subunits and this dimerization is critical for liganding their cognate receptors and execution of proper functions....
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0280137
更新日期:2002-04-01 00:00:00
abstract::Soluble guanylyl cyclase is a cytosolic enzyme which catalyzes conversion of GTP to the second messenger cyclic GMP. The transcriptional regulation at the promoter levels of four soluble guanylyl cyclase subunits, termed alpha1, alpha2, beta1, and beta2, is largely unknown. In this study, we identified the transcripti...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.02180
更新日期:2006-12-01 00:00:00
abstract::Luteotropic glycoprotein hormones (LGH) include luteinizing hormone (LH) and chorionic gonadotropin (CG). The order Primates is the only phylogenetic clad known to exhibit more than one LGHbeta subunit gene per haploid genome. In the present study, we report the discovery of a second case of LGHbeta gene replication, ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0210019
更新日期:1998-08-01 00:00:00
abstract::1alpha,25-dihydroxyvitamin D(3) upregulates tumour necrosis factor superfamily member 11 (TNFSF11) that codes for the receptor activator of nuclear factor kappaB ligand (RANKL), and downregulates osteoprotegerin (OPG) expression. We have analyzed the individual effects of polymorphisms in the vitamin D receptor gene (...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-08-0108
更新日期:2009-03-01 00:00:00
abstract::In vertebrates, sex is determined essentially by two means, genetic factors located on sex chromosomes and epigenetic factors such as temperature experienced by the individual during development. Steroids, especially estrogens, are clearly involved in gonadal differentiation in non-mammalian vertebrates. In this regar...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01588
更新日期:2004-12-01 00:00:00
abstract::The interaction of IGF binding protein-2 (IGFBP-2) with IGF-I and -II has been investigated in solution using nuclear magnetic resonance (NMR) spectroscopy. Chemical shift perturbations in 15N- and 2H/15N-labelled IGF-I or -II upon binding to unlabelled thioredoxin-tagged bovine IGFBP-2 (Trx(1-279)IGFBP-2) have been m...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01756
更新日期:2005-06-01 00:00:00
abstract::Oligonucleotide microarrays were used to analyse gene expression profiles in human ZR75-1 breast cancer cells in the presence of 17beta-oestradiol and oestrogen antagonists. Differential gene expression of a number of genes was confirmed by quantitative RNA analysis. In addition to known oestrogen-responsive genes, an...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0270259
更新日期:2001-12-01 00:00:00
abstract::Gene related to anergy in lymphocytes (GRAIL) is an E3 ubiquitin ligase that regulates energy in T-lymphocytes. Whereas, the relevance of GRAIL to T lymphocyte function is well established, the role of this protein in other cell types remains unknown. Given that GRAIL is abundant in the liver, we investigated the pote...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-08-0145
更新日期:2009-02-01 00:00:00
abstract::Members of the nuclear receptor superfamily of ligand-regulated transcription factors are targets of a wide range of lipophilic signaling molecules as well as several drugs and xenobiotics that modulate many aspects of physiology and metabolism. Agonist binding to receptors is associated with recruitment of coactivato...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1677/jme.0.0310001
更新日期:2003-08-01 00:00:00
abstract::Tight regulation of fatty acid metabolism in pancreatic beta-cells is important for beta-cell viability and function. Chronic exposure to elevated concentrations of fatty acid is associated with beta-cell lipotoxicity. Glucose is known to repress fatty acid oxidation and hence to augment the toxicity of fatty acids. T...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01965
更新日期:2006-04-01 00:00:00
abstract::The presence of retinoic acid receptor (RAR) alpha, beta and gamma mRNA was examined in 16 different kinds of rat tissue using the highly sensitive reverse transcriptase-polymerase chain reaction technique. The data demonstrated that each tissue expressed at least two types of RAR mRNA. Among the three types of RAR mR...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0090291
更新日期:1992-12-01 00:00:00
abstract::In this study we examine changes in the cellular properties of FRTL-5 cells as a function of passage number, with particular emphasis on gap junction expression, karyotype, morphology, growth rate and thyroxine (T(4)) release. Early passage FRTL-5 follicular cells transfer dye through gap junctions from injected cell(...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0270145
更新日期:2001-10-01 00:00:00
abstract::The melanocortin 2 receptor accessory protein (MRAP) was originally discovered to be an essential co-receptor for the ACTH receptor/melanocortin 2 receptor, and it physically interacts with this receptor and is required for receptor trafficking and ligand binding. A related molecule, MRAP2, is mainly expressed in the ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1530/JME-17-0002
更新日期:2017-04-01 00:00:00
abstract::The pancreatic regenerating (reg) gene is proposed to be involved in pancreatic beta-cell growth. Up- or down-regulation of reg gene expression has been shown to parallel variations in beta-cell mass and function in the adult pancreas. In several species at least two nonallelic reg genes have been identified. In this ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0170079
更新日期:1996-08-01 00:00:00
abstract::Successful human embryo implantation requires a proper differentiation of endometrial stromal cells (ESCs) into decidual cells, during a process called decidualization. ESCs express specific molecules, such as prolactin, insulin-like growth factor-binding protein-1 (IGFBP-1) and connexin-43. Decidual cells are also in...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-17-0046
更新日期:2017-10-01 00:00:00
abstract::The mannose 6-phosphate/IGF 2 receptor (IGF2R) is comprised of 15 extra-cellular domains that bind IGF2 and mannose 6-phosphate ligands. IGF2R transports ligands from the Golgi to the pre-lysosomal compartment and thereafter to and from the cell surface. IGF2R regulates growth, placental development, tumour suppressio...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-08-0154
更新日期:2009-04-01 00:00:00
abstract::Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) are regarded as complications of gastro-oesophageal reflux disease, although all the factors that contribute to the development of these lesions are unknown. Acid suppressive drugs are widely used for symptomatic therapy of reflux disease but may induce hy...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-08-0096
更新日期:2009-04-01 00:00:00
abstract::Fatty acids are essential nutrients that contribute to several intracellular functions. Fatty acid synthesis and oxidation are known to be regulated by sterol regulatory element-binding proteins (SREBPs), which play a pivotal role in the regulation of cellular triglyceride synthesis and cholesterol biogenesis. Recent ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1530/JME-17-0289
更新日期:2018-10-01 00:00:00
abstract::This study determined whether twice-daily intrauterine injections of ovine conceptus secretory proteins (oCSP) containing type-I trophoblast interferon (25 micrograms/uterine horn) from day 11 to day 15 post-oestrus (oestrus = day 0) could alter the binding capacities of endometrial receptors for oxytocin, progesteron...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0100185
更新日期:1993-04-01 00:00:00
abstract::The biologically active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (VD3), exerts its tissue-specific actions through binding to its intracellular vitamin D receptor (VDR) which functions as a heterodimer with retinoid X receptor (RXR) to recognize vitamin D response elements (VDRE) and activate target genes. Up...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-19-0229
更新日期:2020-04-01 00:00:00
abstract::Abnormal placental function is well-established as a major cause for poor pregnancy outcome. Placental blood flow within the maternal uteroplacental compartment, the fetoplacental circulation or both is a vital factor in mediating placental function. Impairment in flow in either or both vasculatures is a significant r...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1530/JME-17-0139
更新日期:2018-01-01 00:00:00
abstract::A unique characteristic of the primate adrenal is the ability to produce 19-carbon steroids, often called the adrenal androgens. Although it is clear that the major human adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S), are produced almost solely in the adrenal reticularis, the mechanisms re...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0300287
更新日期:2003-06-01 00:00:00
abstract::cDNA clones coding for rabbit prolactin were isolated from a pituitary library using a rat prolactin RNA probe. One cDNA contained 873 bases including the entire coding sequence of rabbit prolactin, its signal peptide and the 5' and 3' untranslated regions of 44 and 145 nucleotides respectively. The deduced amino acid...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0160027
更新日期:1996-02-01 00:00:00
abstract::The peroxisome proliferator-activated receptor (PPAR) is a member of the steroid hormone receptor superfamily and is activated by a variety of fibrate hypolipidaemic drugs and non-genotoxic rodent hepatocarcinogens that are collectively termed peroxisome proliferators. A key marker of peroxisome proliferator action is...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0110037
更新日期:1993-08-01 00:00:00
abstract::Critical to an understanding of the control of 1,25-dihydroxyvitamin D (1,25D) activity is a molecular appreciation of the regulation of three genes, 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1), 25-hydroxyvitamin D-24-hydroxylase (CYP24) and vitamin D receptor (VDR). We now report the sensitivity, reproducibility...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0310123
更新日期:2003-08-01 00:00:00
abstract::A new full-length cDNA (ZFOR4) that encodes an opioid receptor has been isolated from the teleost zebrafish. The encoded polypeptide is 375 amino acids long and shows high sequence similarity to other delta-opioid receptors, including ZFOR1, the other delta-opioid receptor from zebrafish previously characterized by us...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.02136
更新日期:2006-12-01 00:00:00
abstract::The development and growth of prostate cancer is dependent on androgens; thus, the identification of androgen-regulated genes in prostate cancer cells is vital for defining the mechanisms of prostate cancer development and progression and developing new markers and targets for prostate cancer treatment. Glycine N-meth...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-13-0169
更新日期:2013-11-07 00:00:00
abstract::Human 3beta-hydroxysteroid dehydrogenase/steroid Delta(5)-Delta(4)-isomerase (3beta-HSD/isomerase) is a bifunctional, single enzyme protein that is membrane-bound in the endoplasmic reticulum (microsomes) and mitochondria of cells in the placenta (type I) and in the adrenals and gonads (type II). Two membrane-binding ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0230231
更新日期:1999-10-01 00:00:00
abstract::It has been suggested that the thyroid itself may contribute to the inflammatory process observed in autoimmune thyroiditis by releasing the cytokines interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8), but studies of cytokine gene expression in thyrocytes have been limited and conflicting...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0150011
更新日期:1995-08-01 00:00:00
abstract::Microarray studies have identified many genes that are down-regulated in uterine leiomyoma compared with myometrium, including early growth response gene-1 (EGR1). However, the mechanisms underlying coordinated down-regulation of this gene cohort remain unknown. To address the transcriptional role of EGR1 in leiomyoma...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-06-0069
更新日期:2007-11-01 00:00:00