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	Yoko Obata, Tomoya Nishino, Toshihiro Kushibiki, Ryuji Tomoshige, Zhiyin Xia, Masanobu Miyazaki, Katsushige Abe, Takehiko Koji, Yasuhiko Tabata, Shigeru Kohno
Journal	Acta biomaterialia (Acta Biomater) Vol. 8 Issue 7 Pg. 2688-96 (Jul 2012) ISSN: 1878-7568 [Electronic] England
PMID	22487929 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Chemical References	Actins Cations Ccl2 protein, mouse Chemokine CCL2 Collagen Type III HSP47 Heat-Shock Proteins RNA, Small Interfering Transforming Growth Factor beta alpha-smooth muscle actin, mouse Gelatin
Topics	Actins (metabolism) Animals Cations Chemokine CCL2 (metabolism) Collagen Type III (metabolism) Gelatin (chemistry) Gene Silencing HSP47 Heat-Shock Proteins (metabolism) Immunohistochemistry Male Mice Mice, Inbred ICR Microspheres Peritoneal Fibrosis (metabolism, pathology, prevention & control) Peritoneum (metabolism, pathology) RNA, Small Interfering (metabolism) Staining and Labeling Sus scrofa Transforming Growth Factor beta (metabolism)

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