ABSTRACT
Our previous study showed that the adipose afferent reflex (AAR) induced by chemical stimulation of white adipose tissue (WAT) increased sympathetic outflow and blood pressure. We also found that pro-inflammatory cytokines (PICs) in the hypothalamic paraventricular nucleus (PVN) potentiate the cardiac sympathetic afferent reflex in rats. However, the role of PICs in the PVN in regulating the AAR is still not clear. This study determined whether PICs in the PVN mediate the AAR in rats. The AAR was evaluated based on renal sympathetic nerve activity and mean arterial blood pressure in response to capsaicin injection into inguinal WAT (iWAT). PIC levels were measured by ELISA. PVN microinjection with the PICs tumor necrosis factor (TNF)-α or interleukin (IL)-1ß enhanced the AAR in a dose-dependent manner. Furthermore, pretreatment via the bilateral microinjection of the TNF-α-blocker etanercept or IL-1ß blocker IL-1ra into the PVN attenuated the AAR. In rats pretreated with TNF-α or IL-1ß, a sub-response dose of angiotensin II (Ang II) significantly enhanced the AAR. Moreover, delivery of the angiotensin II type 1(AT1) receptor antagonist losartan into the PVN attenuated the effects of TNF-α or IL-1ß on the AAR. In addition, stimulating either iWAT or retroperitoneal WAT with capsaicin increased TNF-α or IL-1ß levels in the PVN, but the injection of capsaicin into the jugular vein, skeletal muscle, and skin had no effects on TNF-α or IL-1ß levels in the PVN. These results suggest that TNF-α or IL-1ß and Ang II in the PVN synergistically enhance the AAR in rats.
Subject(s)
Adipose Tissue, White/metabolism , Cytokines/metabolism , Inflammation/metabolism , Paraventricular Hypothalamic Nucleus/metabolism , Reflex/physiology , Adipose Tissue, White/drug effects , Angiotensin II/pharmacology , Animals , Blood Pressure/drug effects , Blood Pressure/physiology , Heart/drug effects , Heart/physiology , Interleukin-1beta/metabolism , Kidney/drug effects , Kidney/metabolism , Losartan/pharmacology , Paraventricular Hypothalamic Nucleus/drug effects , Rats , Rats, Sprague-Dawley , Reflex/drug effects , Sympathetic Nervous System/drug effects , Sympathetic Nervous System/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Contact inhibition and its disruption of vascular smooth muscle cells (VSMCs) are important cellular events in vascular diseases. But the underlying molecular mechanisms are unclear. In this study we investigated the roles of microRNAs (miRNAs) in the contact inhibition and its disruption of VSMCs and the molecular mechanisms involved. Rat VSMCs were seeded at 30% or 90% confluence. MiRNA expression profiles in contact-inhibited conï¬uent VSMCs (90% confluence) and non-contact-inhibited low-density VSMCs (30% confluence) were determined. We found that multiple miRNAs were differentially expressed between the two groups. Among them, miR-145 was significantly increased in contact-inhibited VSMCs. Serum could disrupt the contact inhibition as shown by the elicited proliferation of conï¬uent VSMCs. The contact inhibition disruption accompanied with a down-regulation of miR-145. Serum-induced contact inhibition disruption of VSMCs was blocked by overexpression of miR-145. Moreover, downregulation of miR-145 was sufficient to disrupt the contact inhibition of VSMCs. The downregulation of miR-145 in serum-induced contact inhibition disruption was related to the activation PI3-kinase/Akt pathway, which was blocked by the PI3-kinase inhibitor LY294002. KLF5, a target gene of miR-145, was identified to be involved in miR-145-mediated effect on VSMC contact inhibition disruption, as it could be inhibited by knockdown of KLF5. In summary, our results show that multiple miRNAs are differentially expressed in contact-inhibited VSMCs and in non-contact-inhibited VSMCs. Among them, miR-145 is a critical gene in contact inhibition and its disruption of VSMCs. PI3-kinase/Akt/miR-145/KLF5 is a critical signaling pathway in serum-induced contact inhibition disruption. Targeting of miRNAs related to the contact inhibition of VSMCs may represent a novel therapeutic approach for vascular diseases.
Subject(s)
Contact Inhibition/physiology , MicroRNAs/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Animals , Cell Count , Cell Proliferation/physiology , Chromones/pharmacology , Down-Regulation , Kruppel-Like Transcription Factors/metabolism , Male , MicroRNAs/genetics , Morpholines/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Rats, Sprague-Dawley , Signal Transduction/physiologyABSTRACT
The granule-bound starch synthase(GBSS) is encoded by the rice Wx gene, which is the major gene for control of amylase synthesis of. This paper briefly introduced the progress in regulation of rice Wx gene expression at transcriptional level and post-transcriptional level. At the same time the influence of transgene, genetic background and temperature condition on Wx gene expression in rice was discussed. Finally some urgent questions were suggested for the further study on regulation of rice Wx gene expression.