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 that they may have the most similar developmental origins.
authors.affiliation: Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm, Sweden. Electronic address: souren.mkrtchian@ki.se.
authors.forename: Souren
authors.initials: S
authors.lastname: Mkrtchian
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore. Electronic address: csilkl@nus.edu.sg.
authors.forename: Kian Leong
authors.initials: KL
authors.lastname: Lee
authors.affiliation: Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm, Sweden; Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kåhlin
authors.affiliation: Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Anette
authors.initials: A
authors.lastname: Ebberyd
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore; Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Poellinger
authors.affiliation: Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm, Sweden; Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Malin Jonsson
authors.initials: MJ
authors.lastname: Fagerlund
authors.affiliation: Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm, Sweden; Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Lars I
authors.initials: LI
authors.lastname: Eriksson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002344:Carotid Body / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D010100:Oxygen
keywords: Carotid body; Hypoxia; microRNA