title: δ-Opioid Receptor Activation and MicroRNA Expression in the Rat Heart Under Prolonged Hypoxia.
abstract: BACKGROUND
  Hypoxic/ischemic injury to the heart is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ischemic events, and δ-opioid receptor (DOR) activation is known to protect against hypoxic/ischemic injury, we speculated on the involvement of DOR activation in altering miRNA expression in the heart under hypoxic conditions. The present study aimed to test our hypothesis.
  
  
  METHODS
  Male Sprague Dawley rats were exposed to hypoxia (9.5-10% O2) for 1, 5, or 10 days with or without DOR activation. The target miRNAs were selected from TaqMan low-density array (TLDA) data and were further analyzed by quantitative real-time PCR.
  
  
  RESULTS
  We found that: 1) hypoxia alters the miRNA expression profiles depending on the hypoxic duration; 2) DOR activation shifts miRNA expression profiles in normoxic conditions and upregulates miR-128a-3p, miR-134-5p, miR-135a, miR-193a-3p, miR-196a, miR-324-3p, and miR-338; and 3) DOR activation modifies hypoxia-induced changes in miRNA expression and increases the levels of miR-128a-3p, miR-134-5p, miR-135a, miR-193a-3p, miR-196a, miR-324-3p, miR-141, miR-200b, and miR-324-3p. For example, miR-196c-5p decreased by 50% while miR-135a-5p increased 2.9 fold after 10 days under hypoxic conditions. Moreover, DOR activation further strengthened the hypoxia-induced increase of the levels of miR-7a-5p. When DOR was activated using UFP-512, the level of miR-107-3p significantly increased 1 day after the administration of UFP-512, but gradually decreased back to normal under normoxia.
  
  
  CONCLUSIONS
  Hypoxia significantly modifies the miRNA profile in the heart, which can be mimicked or modified by DOR activation. Defining the targeted pathways that regulate the diverse cellular and molecular functions of miRNAs may provide new insights into potential therapies for hypoxic/ischemic injury of the heart.
authors: Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors: Feng
authors: F
authors: Zhi
authors: Lian
authors: L
authors: Xue
authors: Naiyuan
authors: N
authors: Shao
authors: Danni
authors: D
authors: Deng
authors: Xuezhi
authors: X
authors: Kang
authors: Dongman
authors: D
authors: Chao
authors: Yuan
authors: Y
authors: Xu
authors: Rong
authors: R
authors: Wang
authors: Yilin
authors: Y
authors: Yang
authors: Ying
authors: Y
authors: Xia
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C526539:2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1H-benzimidazol-2-yl)(carboxymethyl)methylamide; D001562:Benzimidazoles; D035683:MicroRNAs; D009842:Oligopeptides; D017465:Receptors, Opioid, delta