ABSTRACT
Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understanding the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI). This is followed by a discussion of regulatory mechanisms underlying CDI and NDI, with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R) and the water channel molecule, aquaporin 2 (AQP2). The clinical manifestation, diagnosis, and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.
Subject(s)
Aquaporins , Diabetes Insipidus, Nephrogenic , Diabetes Insipidus , Diabetes Mellitus , Animals , Aquaporin 2/genetics , Aquaporin 2/metabolism , Diabetes Insipidus, Nephrogenic/genetics , Diabetes Insipidus, Nephrogenic/metabolism , Diabetes Insipidus/diagnosis , Diabetes Insipidus/genetics , Aquaporins/genetics , Aquaporins/metabolism , Kidney/metabolism , Water/metabolism , Mutation , Receptors, Vasopressin/genetics , Receptors, Vasopressin/metabolismABSTRACT
OBJECTIVE: The aim of this study was to clarify the role of long non-coding RNA (lncRNA) HOXA-AS2 in influencing the proliferative, migratory and apoptotic abilities of human aortic vascular smooth muscle cells (HA-VSMCs) by absorbing microRNA-877-3p (miRNA-877-3p). MATERIALS AND METHODS: HOXA-AS2 level in HA-VSMCs treated with different doses of oxidized low-density lipoprotein (ox-LDL) and for different time points was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). After transfection of si-HOXA-AS2 in HA-VSMCs undergoing ox-LDL treatment, the viability, apoptotic rate and migration of cells were detected, respectively. Meanwhile, the subcellular distribution of HOXA-AS2 was analyzed. The Dual-Luciferase reporter gene assay was applied to verify the binding relationship between HOXA-AS2 and miRNA-877-3p. MiRNA-877-3p level in HA-VSMCs treated with different doses of ox-LDL was determined as well. Furthermore, the regulatory effects of HOXA-AS2/miRNA-877-3p axis on cellular behaviors of HA-VSMCs were determined. RESULTS: HOXA-AS2 expression was upregulated by ox-LDL treatment in a time- and dose-dependent manner. After being treated with 100 mg/L ox-LDL for 48 h, the proliferative and migratory abilities of HA-VSMCs were significantly enhanced, while apoptosis was inhibited. Conversely, these changes were reversed by transfection of si-HOXA-AS2. HOXA-AS2 was mainly distributed in the nuclear fraction. Dual-Luciferase reporter gene assay confirmed the direct binding relationship between HOXA-AS2 and miRNA-877-3p. Moreover, miRNA-877-3p was markedly downregulated after transfection of si-HOXA-AS2. MiRNA-877-3p expression decreased gradually with an increased dose of ox-LDL. In addition, knockdown of miRNA-877-3p could reverse the regulatory effects of HOXA-AS2 on proliferative, migratory and apoptotic abilities of HA-VSMCs. CONCLUSIONS: HOXA-AS2 is upregulated after HA-VSMCs injury, which accelerates the proliferative and migratory abilities, and inhibits the apoptosis of vascular smooth muscle cells by absorbing miRNA-877-3p.
Subject(s)
Apoptosis , MicroRNAs/metabolism , Muscle, Smooth, Vascular/metabolism , RNA, Long Noncoding/metabolism , Cell Movement , Cell Proliferation , Cells, Cultured , Humans , MicroRNAs/genetics , Muscle, Smooth, Vascular/pathology , RNA, Long Noncoding/geneticsABSTRACT
Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understand the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI ) . This is followed by a discussion of regulatory mechanisms underlying CDI and NDI , with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R ) and the water channel molecule, aquaporin 2 (AQP2 ). The clinical manifestation, diagnosis and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.
