MicroRNA expression profiling in peritoneal fibrosis

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• 作者：Yoshiyuki Morishita^a ; ^{ymori@jichi.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Hiromichi Yoshizawa^b ; Minami Watanabe^b ; Reika Imai^b ; Toshimi Imai^b ; Ichiro Hirahara^b ; Tetsu Akimoto^b ; Susumu Ookawara^a ; Shigeaki Muto^b ; Daisuke Nagata^b
• 关键词：α-SMA ; α-smooth muscle actin ; DAPI ; 4&prime ; 6-diamidino-2-phenylindole ; FGF ; fibroblast growth factor ; FSP-1 ; fibroblast-specific protein-1 ; MGO ; methylglyoxal ; miRNA ; microRNA ; PD ; peritoneal dialysis ; PDF ; peritoneal dialysis fluid ; PET ; peritoneal equilibrium test ; PF ; peritoneal fibrosis ; PPAR-α ; peroxisome proliferator&ndash ; activated receptor-α ; qRT-PCR ; real-time reverse-transcription polymerase chain reaction ; siRNA ; small interfering RNA ; TGF-β1 ; transforming growth factor-β1 ; VEGF ; va
• 刊名：Translational Research
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：169
• 期：Complete
• 页码：47-66
• 全文大小：4303 K

文摘

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.