title: HSP47 siRNA conjugated with cationized gelatin microspheres suppresses peritoneal fibrosis in mice.
abstract: Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for the biosynthesis and secretion of collagen and is expressed in the fibrotic peritoneum. In the present study, we evaluated the efficacy of HSP47 small interfering RNA (siRNA) to suppress the development of peritoneal fibrosis induced by chlorhexidine gluconate in mice. We initially confirmed that biodegradable cationized gelatin microspheres (CGMs) containing HSP47 siRNA could continuously release siRNA over 21 days as a result of microsphere degradation. We then determined that a single injection of CGMs incorporating HSP47 siRNA suppressed collagen expression and macrophage infiltration, thereby preventing peritoneal fibrosis. Therefore, we suggest that this controlled-release technology using HSP47 siRNA is a potential treatment for peritoneal fibrosis. Additionally, RNA interference combined with CGMs as a drug-delivery system may lead to new strategies for knocking down specific genes in vivo.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Obata
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nishino
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kushibiki
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tomoshige
authors.forename: Zhiyin
authors.initials: Z
authors.lastname: Xia
authors.forename: Masanobu
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Katsushige
authors.initials: K
authors.lastname: Abe
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002412:Cations; D018932:Chemokine CCL2 / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D005780:Gelatin / Q000737:chemistry*; D020868:Gene Silencing; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008863:Microspheres; D056627:Peritoneal Fibrosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism*; D013194:Staining and Labeling; D034421:Sus scrofa; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000199:Actins; D002412:Cations; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D024061:Collagen Type III; D050958:HSP47 Heat-Shock Proteins; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; C544013:alpha-smooth muscle actin, mouse; D005780:Gelatin