PMID- 26719145
OWN - NLM
STAT- MEDLINE
DCOM- 20160801
LR  - 20200930
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 310
IP  - 5
DP  - 2016 Mar 1
TI  - Regulation of alveolar septation by microRNA-489.
PG  - L476-87
LID - 10.1152/ajplung.00145.2015 [doi]
AB  - MicroRNAs (miRs) are small conserved RNA that regulate gene expression. 
      Bioinformatic analysis of miRNA profiles during mouse lung development indicated 
      a role for multiple miRNA, including miRNA-489. miR-489 increased on completion 
      of alveolar septation [postnatal day 42 (P42)], associated with decreases in its 
      conserved target genes insulin-like growth factor-1 (Igf1) and tenascin C (Tnc). 
      We hypothesized that dysregulation of miR-489 and its target genes Igf1 and Tnc 
      contribute to hyperoxia-induced abnormal lung development. C57BL/6 mice were 
      exposed to normoxia (21%) or hyperoxia (85% O2) from P4 to P14, in combination 
      with intranasal locked nucleic acid against miR-489 to inhibit miR-489, 
      cytomegalovirus promoter (pCMV)-miR-489 to overexpress miR-489, or empty vector. 
      Hyperoxia reduced miR-489 and increased Igf1 and Tnc. Locked nucleic acid against 
      miR-489 improved lung development during hyperoxia and did not alter it during 
      normoxia, whereas miR-489 overexpression inhibited lung development during 
      normoxia. The 3' untranslated region in vitro reporter studies confirmed Igf1 and 
      Tnc as targets of miR-489. While miR-489 was of epithelial origin and present in 
      exosomes, its targets Igf1 and Tnc were produced by fibroblasts. Infants with 
      bronchopulmonary dysplasia (BPD) had reduced lung miR-489 and increased Igf1 and 
      Tnc compared with normal preterm or term infants. These results suggest increased 
      miR-489 is an inhibitor of alveolar septation. During hyperoxia or BPD, reduced 
      miR-489 and increased Igf1 and Tnc may be inadequate attempts at compensation. 
      Further inhibition of miR-489 may permit alveolar septation to proceed. The use 
      of specific miRNA antagonists or agonists may be a therapeutic strategy for 
      inhibited alveolarization, such as in BPD.
CI  - Copyright (c) 2016 the American Physiological Society.
FAU - Olave, Nelida
AU  - Olave N
AD  - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, 
      Alabama;
FAU - Lal, Charitharth V
AU  - Lal CV
AD  - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, 
      Alabama;
FAU - Halloran, Brian
AU  - Halloran B
AD  - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, 
      Alabama;
FAU - Pandit, Kusum
AU  - Pandit K
AD  - Division of Pulmonary, Allergy and Critical Care Medicine, University of 
      Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
FAU - Cuna, Alain C
AU  - Cuna AC
AD  - Department of Pediatrics, University of Missouri-Kansas City School of Medicine, 
      Kansas City, Missouri;
FAU - Faye-Petersen, Ona M
AU  - Faye-Petersen OM
AD  - Department of Pathology, University of Alabama at Birmingham, Birmingham, 
      Alabama;
FAU - Kelly, David R
AU  - Kelly DR
AD  - Department of Pathology, University of Alabama at Birmingham, Birmingham, 
      Alabama;
FAU - Nicola, Teodora
AU  - Nicola T
AD  - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, 
      Alabama;
FAU - Benos, Panayiotis V
AU  - Benos PV
AD  - Department of Computational & Systems Biology, University of Pittsburgh, 
      Pittsburgh, Pennsylvania; and.
FAU - Kaminski, Naftali
AU  - Kaminski N
AD  - Division of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, 
      New Haven, Connecticut.
FAU - Ambalavanan, Namasivayam
AU  - Ambalavanan N
AD  - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, 
      Alabama; Department of Pathology, University of Alabama at Birmingham, 
      Birmingham, Alabama; nambalavanan@peds.uab.edu.
LA  - eng
GR  - R01 HL-095397/HL/NHLBI NIH HHS/United States
GR  - R01 LM-009657/LM/NLM NIH HHS/United States
GR  - R01 HL-129907/HL/NHLBI NIH HHS/United States
GR  - U01 HL122626/HL/NHLBI NIH HHS/United States
GR  - R01 HL-092906/HL/NHLBI NIH HHS/United States
GR  - U01 HL-122626/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20151230
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (MIRN489 microRNA, human)
RN  - 0 (MIRN489 microRNA, mouse)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Bronchopulmonary Dysplasia/metabolism
MH  - Cell Proliferation/genetics/physiology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Fibroblasts/metabolism
MH  - Humans
MH  - Hyperoxia/*metabolism
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*genetics
MH  - Pulmonary Alveoli/*metabolism
PMC - PMC4773841
OTO - NOTNLM
OT  - infant
OT  - lung development
OT  - microRNAs
OT  - newborn
EDAT- 2016/01/01 06:00
MHDA- 2016/08/02 06:00
PMCR- 2017/03/01
CRDT- 2016/01/01 06:00
PHST- 2015/05/06 00:00 [received]
PHST- 2015/12/26 00:00 [accepted]
PHST- 2017/03/01 00:00 [pmc-release]
PHST- 2016/01/01 06:00 [entrez]
PHST- 2016/01/01 06:00 [pubmed]
PHST- 2016/08/02 06:00 [medline]
AID - ajplung.00145.2015 [pii]
AID - L-00145-2015 [pii]
AID - 10.1152/ajplung.00145.2015 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2016 Mar 1;310(5):L476-87. doi: 
      10.1152/ajplung.00145.2015. Epub 2015 Dec 30.