An inhibitor of Kruppel-like factor 5 suppresses peritoneal fibrosis in mice

被引:3
|
作者
Muta, Kumiko [1 ]
Nakazawa, Yuka [2 ]
Obata, Yoko [1 ,3 ]
Inoue, Hiro [1 ]
Torigoe, Kenta [1 ]
Nakazawa, Masayuki [4 ]
Abe, Katsushige [5 ]
Furusu, Akira [6 ]
Miyazaki, Masanobu [7 ]
Yamamoto, Kazuo [8 ]
Koji, Takehiko [9 ]
Nishino, Tomoya [1 ]
机构
[1] Nagasaki Univ Hosp, Dept Nephrol, 1-7-1 Sakamoto, Nagasaki 8528501, Japan
[2] Hokusyo Cent Hosp, Dept Nephrol, Nagasaki, Japan
[3] Nagasaki Univ Hosp, Med Educ Dev Ctr, Nagasaki, Japan
[4] Sasebo City Cent Hosp, Dept Nephrol, Nagasaki, Japan
[5] Jiikai Hosp, Oita, Japan
[6] Wajinkai Hosp, Dept Nephrol, Nagasaki, Japan
[7] Miyazaki Clin, Nagasaki, Japan
[8] Nagasaki Univ, Sch Med, Biomed Res Support Ctr, Nagasaki, Japan
[9] Nagasaki Univ, Grad Sch Biomed Sci, Dept Histol & Cell Biol, Nagasaki, Japan
来源
PERITONEAL DIALYSIS INTERNATIONAL | 2021年 / 41卷 / 04期
关键词
Am80; an inhibitor of KLF5; peritoneal dialysis; peritoneal fibrosis; STRESS-PROTEIN HSP47; TRANSCRIPTION FACTOR; EXPRESSION; MEMBRANE; KLF5/BTEB2; REGULATOR; FAMILY; BTEB2; KLF5;
D O I
10.1177/0896860820981322
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Back ground: Kruppel-like transcription factor 5 (KLF5) is a transcription factor regulating cell proliferation, angiogenesis and differentiation. It has been recently reported that Am80, a synthetic retinoic acid receptor alpha-specific agonist, inhibits the expression of KLF5. In the present study, we have examined the expression of KLF5 in fibrotic peritoneum induced by chlorhexidine gluconate (CG) in mouse and evaluated that Am80, as an inhibitor of KLF5, can reduce peritoneal fibrosis. Methods: Peritoneal fibrosis was induced by intraperitoneal injection of CG into peritoneal cavity of ICR mice. Am80 was administered orally for every day from the start of CG injection. Control mice received only a vehicle (0.5% carboxymethylcellulose solution). After 3 weeks of treatment, peritoneal equilibration test (PET) was performed and peritoneal tissues were examined by immunohistochemistry. Results: The expression of KLF5 was less found in the peritoneal tissue of control mice, while KLF5 was expressed in the thickened submesothelial area of CG-injected mice receiving the vehicle. Am80 treatment reduced KLF5 expression and remarkably attenuated peritoneal thickening, accompanied with the reduction of type III collagen expression. The numbers of transforming growth factor beta-positive cells, alpha-smooth muscle actin-positive cells and infiltrating macrophages were significantly decreased in Am80-treated group. PET revealed the increased peritoneal permeability in CG mice, whereas Am80 administration significantly improved the peritoneal high permeability state. Conclusions: These results indicate the involvement of KLF5 in the progression of experimental peritoneal fibrosis and suggest that Am80 may be potentially useful for the prevention of peritoneal fibrosis through inhibition of KLF5 expression.
引用
收藏
页码:394 / 403
页数:10
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