Hu Delin, Yu Youxin, Wang Chunhua, Li Denghui, Tai Yuncheng, Fang Linsen
Department of Burns, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui Province, 230022, People's Republic of China.
Eur J Med Res. 2015 Apr 23;20(1):51. doi: 10.1186/s40001-015-0141-5.
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.
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.
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).
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.
微小RNA是一种小的非编码RNA分子，在RNA沉默和基因表达的转录后调控中发挥作用。本研究旨在评估miR-98在微血管通透性发展及其分子发病机制中的作用。
将48只健康成年Wistar大鼠分为对照组（n = 8）和烧伤组（n = 40），烧伤组造成30%体表面积的三度烧伤。在烧伤后2、4、8、12和24小时对各组进行处理。从对照组和烧伤后12小时的大鼠收集用于血管内皮细胞培养的血浆。测量有机微血管通透性和血清miR-98水平。在体外，用烧伤血清刺激大鼠主动脉内皮细胞。测定miR-98水平以及缺氧诱导因子-1（HIF-1）、抑制HIF-1α的因子（FIH-1）和紧密连接相关蛋白的蛋白水平。
烧伤后2小时有机微血管通透性开始升高，除肺组织在12小时仍在升高外，在整个实验过程中保持相同特征；血清miR-98水平升高（P < 0.05）。在体外，烧伤血清刺激增加了大鼠主动脉内皮单层细胞的通透性，并上调了miR-98表达（P < 0.05）。转染实验结果显示，miR-98负调控FIH-1和紧密连接相关蛋白的表达（P < 0.05）。
本研究结果表明烧伤导致严重的微血管通透性；其潜在机制基于miR-98水平升高至激活HIF-1基因表达，导致连接相关蛋白缺乏。
