MicroRNA expression profiling in peritoneal fibrosis.
MicroRNA expression profiling in peritoneal fibrosis.
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DOI：
10.1016/j.trsl.2015.10.009
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Yoshiyuki Morishita;Hiromichi Yoshizawa;Minami Watanabe;Reika Imai;T. Imai;I. Hirahara;T. Akimoto;S. Ookawara;S. Muto;D. Nagata
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文献类型：
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作者：
Yoshiyuki Morishita;Hiromichi Yoshizawa;Minami Watanabe;Reika Imai;T. Imai;I. Hirahara;T. Akimoto;S. Ookawara;S. Muto;D. Nagata
腹膜纤维化（PF）是腹膜透析（PD）中导致腹膜衰竭的难治性并发症。本研究的目的是鉴定与PF有关的microrna (miRNA)，使用微阵列分析筛选PF大鼠模型腹膜组织的miRNA表达。通过腹膜平衡试验，对33例PD患者的血清和排出的透析液中差异表达mirna的表达水平进行了评估，并与腹膜功能相关。此外，将miRNA抑制剂（抗miRNA-21-5p锁定核酸（LNA）：抗miRNA-21-LNA）腹腔注射PF模型小鼠，研究其对PF的影响。对PF大鼠腹膜组织进行初步分析，发现6种miRNA （miRNA-142-3p、miRNA-21-5p、miRNA-221-3p、miRNA-223-3p、miRNA-34a-5p和miRNA-327）表达增加2倍以上，没有表达减少一半以上的miRNA。其中，血清miRNA-21-5p、miRNA-221-3p、miRNA-327水平及透析液中miRNA-221-3p、miRNA-34a-5p水平与PD患者腹膜功能显著相关。抗mirna -21- lna显著抑制PF小鼠腹膜中miRNA-21-5p的表达，抑制腹膜纤维增厚，维持腹膜功能。这些结果表明，有几种mirna参与了PF，它们可能作为PF的新的诊断生物标志物和治疗靶点。
Peritoneal fibrosis (PF) is an intractable complication leading to peritoneal membrane failure in peritoneal dialysis (PD). The aim of this study was to identify microRNAs (miRNAs) involved in PF. Peritoneal tissue from a PF rat model was screened for miRNA expression using microarray analysis. The expression levels of differentially expressed miRNAs were evaluated in serum and drained dialysate and associated with peritoneal membrane functions, as measured by the peritoneal equilibrium test in 33 PD patients. Furthermore, an miRNA inhibitor (anti–miRNA-21-5p locked nucleic acid (LNA): anti–miRNA-21-LNA) was intraperitoneally injected to PF model mice to investigate its effects on PF. The initial profiling study of PF rat peritoneal tissue identified 6 miRNAs (miRNA-142-3p, miRNA-21-5p, miRNA-221-3p, miRNA-223-3p, miRNA-34a-5p, and miRNA-327) whose expression was increased more than 2-fold and no miRNAs whose expression was decreased more than half. Among them, serum levels of miRNA-21-5p, miRNA-221-3p, and miRNA-327 and drained dialysate levels of miRNA-221-3p and miRNA-34a-5p were significantly correlated with peritoneal membrane functions in PD patients. Anti–miRNA-21-LNA significantly inhibited miRNA-21-5p expression in the PF mouse peritoneum, inhibited peritoneal fibrous thickening, and maintained peritoneal membrane functions. These results suggest that several miRNAs are involved in PF and that they may be useful as novel diagnostic biomarkers and therapeutic targets for PF.