Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
Acta Biomater. 2012 Jul;8(7):2688-96. doi: 10.1016/j.actbio.2012.03.050. Epub 2012 Apr 6.
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.
热休克蛋白 47(HSP47)是一种胶原特异性分子伴侣,对于胶原的生物合成和分泌至关重要,并在纤维化的腹膜中表达。在本研究中,我们评估了 HSP47 小干扰 RNA(siRNA)抑制葡萄糖酸氯己定诱导的小鼠腹膜纤维化发展的疗效。我们最初证实,含有 HSP47 siRNA 的可生物降解的阳离子化明胶微球(CGMs)由于微球降解可以在 21 天内持续释放 siRNA。然后,我们确定单次注射 HSP47 siRNA 的 CGMs 抑制了胶原表达和巨噬细胞浸润,从而预防了腹膜纤维化。因此,我们认为这种使用 HSP47 siRNA 的控释技术是治疗腹膜纤维化的一种有潜力的方法。此外,RNA 干扰与 CGM 作为药物递送系统相结合可能会为体内敲低特定基因带来新的策略。