1. Academic Validation
  2. Potential Efficacy of Proteasome Inhibitor, Delanzomib, for the Treatment of Renal Fibrosis

Potential Efficacy of Proteasome Inhibitor, Delanzomib, for the Treatment of Renal Fibrosis

  • Biol Pharm Bull. 2023;46(2):279-285. doi: 10.1248/bpb.b22-00713.
Ayano Sawa-Aihara 1 2 Katsuji Hattori 2 Goshi Nagao 2 Yoshihisa Yamada 2 Tatsuhiro Ishida 1
Affiliations

Affiliations

  • 1 Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University.
  • 2 Department of Renal and Cardiovascular Research, Otsuka Pharmaceutical Co., Ltd.
Abstract

Renal fibrosis is scarring and tissue hardening caused by the excess deposition of extracellular matrix proteins in response to chronic inflammation. Renal fibrosis is the primary cause of a progressive loss of renal function, and is an important therapeutic target because it ultimately leads to end-stage renal failure, which can be treated only by either dialysis or kidney transplantation. There is no effective treatment that specifically targets renal fibrosis. Myofibroblasts are known to evade Apoptosis by activating molecular mechanisms in response to pro-survival biomechanical and growth factor signals from the fibrotic microenvironment. In this study, we screened and selected compounds that selectively cause cell death in myofibroblasts in vitro and studied their possible potency against renal fibrosis in a mouse model. Several Proteasome inhibitors induced selective cell death in myofibroblasts differentiated from the human fibroblast cell line (MRC5). The in vivo antifibrotic effect of Delanzomib (Dz), one of the Proteasome inhibitors most sensitive to myofibroblasts in vitro, was investigated in a Unilateral Ureteric Obstruction (UUO) mouse model. Treatment with Dz decreased the expression levels of the actin-alpha-2 (ACTA2) and collagen-type-1-alpha-1 (COL1A1) genes in the kidney, which are common fibrosis markers. These results suggest that Dz might be a compound that suppresses renal fibrosis by inducing selective cell death of myofibroblasts, although further investigation is required.

Keywords

Delanzomib; fibrosis; kidney.

Figures
Products
我们的 Cookie 政策

我们使用 Cookies 和类似技术以提高网站的性能和提升您的浏览体验,部分功能也使用 Cookies 帮助我们更好地理解您的需求,为您提供相关的服务。 如果您有任何关于我们如何处理您个人信息的疑问,请阅读我们的《隐私声明》