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Title: Hypoxia regulates microRNA expression in the human carotid body

Abstract

The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating thatmore » they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.« less

Authors:
 [1];  [2];  [1];  [3];  [1];  [2];  [3]; ;  [1];  [3]
  1. Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden)
  2. Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore (Singapore)
  3. (Sweden)
Publication Date:
OSTI Identifier:
22649846
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 352; Journal Issue: 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; ANIMALS; ANOXIA; APOPTOSIS; BIOLOGICAL PATHWAYS; BIOLOGICAL RECOVERY; BRAIN; CELL DIFFERENTIATION; CELL PROLIFERATION; GENES; HOMEOSTASIS; LEAD; OXYGEN; REGULATIONS; RESPONSE FUNCTIONS; RNA; SURGERY

Citation Formats

Mkrtchian, Souren, E-mail: souren.mkrtchian@ki.se, Lee, Kian Leong, E-mail: csilkl@nus.edu.sg, Kåhlin, Jessica, Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm, Ebberyd, Anette, Poellinger, Lorenz, Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Fagerlund, Malin Jonsson, Eriksson, Lars I., and Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm. Hypoxia regulates microRNA expression in the human carotid body. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2017.02.027.
Mkrtchian, Souren, E-mail: souren.mkrtchian@ki.se, Lee, Kian Leong, E-mail: csilkl@nus.edu.sg, Kåhlin, Jessica, Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm, Ebberyd, Anette, Poellinger, Lorenz, Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Fagerlund, Malin Jonsson, Eriksson, Lars I., & Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm. Hypoxia regulates microRNA expression in the human carotid body. United States. doi:10.1016/J.YEXCR.2017.02.027.
Mkrtchian, Souren, E-mail: souren.mkrtchian@ki.se, Lee, Kian Leong, E-mail: csilkl@nus.edu.sg, Kåhlin, Jessica, Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm, Ebberyd, Anette, Poellinger, Lorenz, Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Fagerlund, Malin Jonsson, Eriksson, Lars I., and Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm. Wed . "Hypoxia regulates microRNA expression in the human carotid body". United States. doi:10.1016/J.YEXCR.2017.02.027.
@article{osti_22649846,
title = {Hypoxia regulates microRNA expression in the human carotid body},
author = {Mkrtchian, Souren, E-mail: souren.mkrtchian@ki.se and Lee, Kian Leong, E-mail: csilkl@nus.edu.sg and Kåhlin, Jessica and Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm and Ebberyd, Anette and Poellinger, Lorenz and Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm and Fagerlund, Malin Jonsson and Eriksson, Lars I. and Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm},
abstractNote = {The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.},
doi = {10.1016/J.YEXCR.2017.02.027},
journal = {Experimental Cell Research},
number = 2,
volume = 352,
place = {United States},
year = {Wed Mar 15 00:00:00 EDT 2017},
month = {Wed Mar 15 00:00:00 EDT 2017}
}