Up-regulation of selenoprotein P and HIP/PAP mRNAs in hepatocytes by intermittent hypoxia via down-regulation of miR-203
نویسندگان
چکیده
Sleep apnea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]) and is a risk factor for insulin resistance/type 2 diabetes. However, the mechanisms linking IH stress and insulin resistance remain elusive. We exposed human hepatocytes (JHH5, JHH7, and HepG2) to experimental IH or normoxia for 24 h, measured mRNA levels by real-time reverse transcription polymerase chain reaction (RT-PCR), and found that IH significantly increased the mRNA levels of selenoprotein P (SELENOP) - a hepatokine - and hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) - one of REG (Regenerating gene) family. We next investigated promoter activities of both genes and discovered that they were not increased by IH. On the other hand, a target mRNA search of micro RNA (miRNA) revealed that both mRNAs have a potential target sequence for miR-203. The miR-203 level of IH-treated cells was significantly lower than that of normoxia-treated cells. Thus, we introduced miR-203 inhibitor and a non-specific control RNA (miR-203 inhibitor NC) into HepG2 cells and measured the mRNA levels of SELENOP and HIP/PAP. The IH-induced expression of SELENOP and HIP/PAP was abolished by the introduction of miR-203 inhibitor but not by miR-203 inhibitor NC. These results demonstrate that IH stress up-regulates the levels of SELENOP in human hepatocytes to accelerate insulin resistance and up-regulates the levels of HIP/PAP mRNAs to proliferate such hepatocytes, via the miR-203 mediated mechanism.
منابع مشابه
Quercetin protects PC-12 cells against hypoxia injury by down-regulation of miR-122
Objective(s): Impairment of nerve cells of brain induced by hypoxia results in energy-deprivation and dysfunction, which accompanies with neurons apoptosis. Improving function of nerve cells is important for treating cerebral anoxia. This study aimed to investigate the role of Quercetin (Quer) in hypoxia-induced injury of pheochromocytoma (PC-12) cells. Materials and Methods: PC-12 cells were c...
متن کاملThe protective effect of bone marrow-derived mesenchymal stem cells in liver ischemia/reperfusion injury via down-regulation of miR-370
Objective(s): Liver transplantation is the most important therapy for end-stage liver disease and ischemia reperfusion (I/R) injury is indeed a risk factor for hepatic failure after grafting. The role of miRNAs in I/R is not completely understood. The aim of this study was to investigate the potential protective role of the mesenchymal stem cells (MSCs) and ischemic pr...
متن کاملInhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1α in rats
Objective(s): The aim of this study was to identify the role of miR-155 in the myocardial ischemia/reperfusion (I/R) injury through targeting hypoxia-inducible factor 1-alpha (HIF-1α). Materials and Methods: We constructed rat models with myocardial I/R injury and H9C2 cell models with hypoxia/reoxygenation (H/R) damage. Anti-miR-155 and...
متن کاملSimultaneous regulation of miR-451 and miR-191 led to erythroid fate decision of mouse embryonic stem cell
Objective(s): Various microRNAs (miRNAs) are expressed during development of mammalian cells, when they aid in modulating gene expression by mediating mRNA transcript cleavage and/or regulation of translation rate. miR-191 and miR-451 have been shown to be critical regulators of hematopoiesis and have important roles in the induction of erythroid fate decision. So, the aim of this study is inve...
متن کاملDown-regulation of miR-193b-3p and miR-376a-3p in Chronic Lymphocytic Leukemia
Background: Chronic lymphocytic leukemia (CLL) is the most common adult human leukemia. Studies revealed that microRNAs (miRNAs) can function as oncogenes or tumor suppressors in CLL and that the expression of miRNAs, such as miR-193b-3p and miR-376a-3p change in several diseases. We aimed to elucidate the changes in miR-193b-3p and miR-376a-3p expression in CLL and determine their potential as...
متن کامل