HSP47 siRNA conjugated with cationized gelatin microspheres suppresses peritoneal fibrosis in mice

Obata, Yoko; Nishino, Tomoya; Kubota, Toshihiro; Tomoshige, Ryuji; Xia, Zihao; Miyazaki, Masanobu; Abe, Katsushige; Koji, Takehiko; Tabata, Yasuhiko; Kohno, Shigeru

doi:10.1016/j.actbio.2012.03.050

Cited by 56 publications

(37 citation statements)

References 46 publications

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“…Previous studies in several experimental animal fibrosis models have shown that downregulation of HSP47 expression reduces production of collagen and subsequently diminishes progression of fibrosis (Sunamoto et al 1998;Nishino et al 2003;Hagiwara et al 2007a, b, c;Obata et al 2012). Therefore, HSP47 may be a novel therapeutic target for patients with AE-IPF.…”

Section: Introductionmentioning

confidence: 99%

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Kakugawa

Yokota

Ishimatsu

et al. 2013

Cell Stress and Chaperones

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Little is known about the pathophysiology of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF). Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for biosynthesis and secretion of collagen molecules. Previous studies in experimental animal fibrosis models have shown that downregulation of HSP47 expression reduces collagen production and diminishes fibrosis progression. In this study, serum HSP47 levels were evaluated to elucidate pathogenic differences involving HSP47 between AE-IPF and stable (S)-IPF. -013-0411-5 and lactate dehydrogenase (LDH) were measured. Immunohistochemical analysis of lung HSP47 expression was determined in biopsy and autopsy tissues diagnosed as diffuse alveolar damage (DAD) and usual interstitial pneumonia (UIP). Serum levels of HSP47 were significantly higher in AE-IPF than in S-IPF patients, whereas serum levels of KL-6, SP-A, and SP-D did not differ significantly. Receiver operating characteristic curves revealed that HSP47 was superior for discriminating AE-IPF and S-IPF. The cutoff for HSP47 resulting in the highest diagnostic accuracy was 559.4 pg/mL; sensitivity, specificity, and diagnostic accuracy were 100.0 %, 93.9 %, and 96.2 %, respectively. Immunohistochemical analysis revealed that pulmonary HSP47 expression was greater in DAD than UIP tissues. Serum HSP47 was significantly higher in AE-IPF than in S-IPF patients, suggesting that underlying fibrogenic mechanisms involving HSP47 differ in the two conditions.Cell Stress and Chaperones (2013) 18:581-590 DOI 10.1007/s12192

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Section: Introductionmentioning

confidence: 99%

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Kakugawa

Yokota

Ishimatsu

et al. 2013

Cell Stress and Chaperones

Self Cite

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“…In addition, their preparation is relatively simple compared with viral vectors. Non-viral vectors used for the treatment of peritoneal fibrosis in vivo include liposome nanoparticles [39], gold nanoparticles [37], and cationic gelatin nanoparticles [40], which have been shown to deliver transgenes to the peritoneum effectively in peritoneal fibrosis animal models and have demonstrated efficacy in vivo (Figure 2) [37,39,40]. …”

Section: Non-viral Vectorsmentioning

confidence: 99%

“…Cationic gelatin nanoparticles are produced chemically by introducing cations such as ethylenediamine, putrescine, spermidine, or spermine to the carboxyl group of gelatin, and have been shown to protect transgenes against degradation in vivo [40]. The release rate of transgenes from cationic gelatin nanoparticles can be modulated by changing the degradability of the gelatins [40].…”

Section: Non-viral Vectorsmentioning

confidence: 99%

“…The release rate of transgenes from cationic gelatin nanoparticles can be modulated by changing the degradability of the gelatins [40]. Cationic gelatin nanoparticles demonstrated therapeutic efficacy in a mouse peritoneal fibrosis model [40]. Intraperitoneal single injection of heat shock protein 47 (HSP47)-siRNA entrapped with cationic gelatin nanoparticles was shown to release HSP47-siRNA continuously over 21 days as a result of degradation of the gelatin nanoparticles [40].…”

Section: Non-viral Vectorsmentioning

confidence: 99%

“…Cationic gelatin nanoparticles demonstrated therapeutic efficacy in a mouse peritoneal fibrosis model [40]. Intraperitoneal single injection of heat shock protein 47 (HSP47)-siRNA entrapped with cationic gelatin nanoparticles was shown to release HSP47-siRNA continuously over 21 days as a result of degradation of the gelatin nanoparticles [40]. They also significantly inhibited both expression of HSP47 in the peritoneum and peritoneal fibrosis, together with decreased expression of type III collagen, TGF-β 1 , α-SMA, and monocyte chemoattractant protein-1 in peritoneal tissue in a mouse peritoneal fibrosis model [40].…”

Section: Non-viral Vectorsmentioning

confidence: 99%

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Nano-sized carriers in gene therapy for peritoneal fibrosisin vivo

Igarashi

Hoshino

Ookawara

et al. 2017

Nano Reviews & Experiments

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Peritoneal fibrosis is a crucial complication in patients receiving peritoneal dialysis. It is a major pathological feature of peritoneal membrane failure, which leads to withdrawal of peritoneal dialysis. No specific therapy has yet been established for the treatment of peritoneal fibrosis. However, gene therapy may be a viable option, and various nano-sized carriers, including viral and non-viral vectors, have been shown to enhance the delivery and efficacy of gene therapy for peritoneal fibrosis in vivo. This review focuses on the use of nano-sized carriers in gene therapy of peritoneal fibrosis in vivo.

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Recent Advances in Engineering Carriers for siRNA Delivery

Yang,

Lin,

Zhang

et al. 2024

Macromolecular Bioscience

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RNA interference (RNAi) technology has been a promising treatment strategy for combating intractable diseases. However, the applications of RNAi in clinical were hampered by extracellular and intracellular barriers. To overcome these barriers, various siRNA delivery systems have been developed in the past two decades. The first approved RNAi therapeutic, Patisiran (ONPATTRO™) using lipids as the carrier, for the treatment of amyloidosis is one of the most important milestones. This has greatly encouraged researchers to work on creating new functional siRNA carriers. In this review, we summarized the recent advances in siRNA carriers consisting of lipids, polymers, and polymer‐modified inorganic particles for cancer therapy. Representative examples are presented to show the structural design of the carriers in order to overcome the delivery hurdles associated with RNAi therapies. Finally, the existing challenges and future perspective for developing RNAi as a clinical modality will be discussed and proposed. We believe that the addressed contributions in this review will promote the development of siRNA delivery systems for future clinical applications.This article is protected by copyright. All rights reserved

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HSP47 siRNA conjugated with cationized gelatin microspheres suppresses peritoneal fibrosis in mice

Cited by 56 publications

References 46 publications

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Nano-sized carriers in gene therapy for peritoneal fibrosisin vivo

Recent Advances in Engineering Carriers for siRNA Delivery

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