title: MicroRNA expression profiling in peritoneal fibrosis.
abstract: 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.
authors.affiliation: Division of Nephrology, Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Omiya, Saitama, Japan. Electronic address: ymori@jichi.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Morishita
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Tochigi, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yoshizawa
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Tochigi, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Tochigi, Japan.
authors.forename: Reika
authors.initials: R
authors.lastname: Imai
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Tochigi, Japan.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Imai
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Tochigi, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirahara
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Tochigi, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akimoto
authors.affiliation: Division of Nephrology, Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Omiya, Saitama, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ookawara
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Tochigi, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Muto
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Tochigi, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nagata
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D056627:Peritoneal Fibrosis / Q000235:genetics*; D017207:Rats, Sprague-Dawley
chemical_list: D035683:MicroRNAs