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International J. Molecular Sciencesに論文が掲載されました。(持続型チオレドキシンによるAKI to CKD抑制効果)

2021/06/03

Recombinant Long-Acting Thioredoxin Ameliorates AKI to CKD Transition via Modulating Renal Oxidative Stress and Inflammation

Kento Nishida 1 , Hiroshi Watanabe 1# , Ryota Murata 1 , Kai Tokumaru 1 , Rui Fujimura 1 , Shun Oshiro 1 , Taisei Nagasaki 1 , Masako Miyahisa 1 , Yuto Hiramoto 1 , Hiroto Nosaki 1 , Tadashi Imafuku 1 , Hitoshi Maeda 1 , Masafumi Fukagawa 2 , Toru Maruyama 1

1 Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
2 Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara 259-1193, Japan.

Abstract

An effective strategy is highly desirable for preventing acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Thioredoxin-1 (Trx), a redox-active protein that has anti-oxidative and anti-inflammatory properties, would be a candidate for this but its short half-life limits its clinical application. In this study, we examined the renoprotective effect of long-acting Trx that is comprised of human albumin and Trx (HSA-Trx) against AKI to CKD transition. AKI to CKD mice were created by renal ischemia-reperfusion (IR). From day 1 to day 14 after renal IR, the recovery of renal function was accelerated by HSA-Trx administration. On day 14, HSA-Trx reduced renal fibrosis compared with PBS treatment. At the early phase of fibrogenesis (day 7), HSA-Trx treatment suppressed renal oxidative stress, pro-inflammatory cytokine production and macrophage infiltration, thus ameliorating tubular injury and fibrosis. In addition, HSA-Trx treatment inhibited G2/M cell cycle arrest and apoptosis in renal tubular cells. While renal Trx protein levels were decreased after renal IR, the levels were recovered by HSA-Trx treatment. Together, HSA-Trx has potential for use in the treatment of AKI to CKD transition via its effects of modulating oxidative stress and inflammation.

Keywords: acute kidney injury; albumin fusion; chronic kidney disease; thioredoxin.