title: microRNA-98 mediated microvascular hyperpermeability during burn shock phase via inhibiting FIH-1.
abstract: BACKGROUND
  microRNA is a small non-coding RNA molecule and functions in RNA silencing and post-transcriptional regulation of gene expression. This study was designed to evaluate the role of miR-98 in the development of microvascular permeability and its molecular pathogenesis.
  
  
  METHODS
  Forty-eight healthy adult Wistar rats were divided into the control group (n = 8) and burn group (n = 40) that inflicted with 30% total body surface area third-degree burn. Groups were processed at 2, 4, 8, 12, and 24 h post-burn. Plasma for vascular endothelial cell culture was collected from control and 12 h post-burn rats. Organic microvascular permeability and serum miR-98 level were measured. In vitro, rat aorta endothelial cells were stimulated with burn serum. Level of miR-98 and protein of hypoxia-inducible factor-1 (HIF-1), factor inhibiting HIF-1α (FIH-1), and tight junction-associated proteins were determined.
  
  
  RESULTS
  Organic microvascular permeability began to rise at 2 h post-burn and maintained the same character throughout the experiment except in lung tissue that was still rising at 12 h; the serum level of miR-98 was elevated (P < 0.05). In vitro, burn serum stimulation increased rat aorta endothelial monolayer cell permeability as well as upregulated miR-98 expression (P < 0.05). As shown in the result of transfection experiment, miR-98 negatively regulated FIH-1 and tight junction-associated protein expression (P < 0.05).
  
  
  CONCLUSIONS
  The findings of the present study suggest severe microvascular permeability due to burns; and the underlying mechanism bases on the promotion of miR-98 level to the extent that it activated HIF-1 gene expression, resulting in junction-associated protein deficiency.
authors.affiliation: Department of Burns, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui Province, 230022, People's Republic of China. Hu_del@163.com.
authors.forename: Delin
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Burns, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui Province, 230022, People's Republic of China. Yyouxin@yeah.net.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Burns, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui Province, 230022, People's Republic of China. Chunh_w@126.com.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Burns, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui Province, 230022, People's Republic of China. Ldengh@126.com.
authors.forename: Denghui
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Burns, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui Province, 230022, People's Republic of China. taiyunc@126.com.
authors.forename: Yuncheng
authors.initials: Y
authors.lastname: Tai
authors.affiliation: Department of Burns, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui Province, 230022, People's Republic of China. fangls@yeah.net.
authors.forename: Linsen
authors.initials: L
authors.lastname: Fang
mesh_terms: D000818:Animals; D002056:Burns / Q000150:complications / Q000378:metabolism*; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D055806:Microvessels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012774:Shock, Traumatic / Q000209:etiology / Q000378:metabolism*; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C571630:MIRN98 microRNA-98, rat; D035683:MicroRNAs; D062725:Tight Junction Proteins