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

• Published in: International journal of molecular sciences Vol. 22; no. 11; p. 5600
• Main Authors: Nishida, Kento, Watanabe, Hiroshi, Murata, Ryota, Tokumaru, Kai, Fujimura, Rui, Oshiro, Shun, Nagasaki, Taisei, Miyahisa, Masako, Hiramoto, Yuto, Nosaki, Hiroto, Imafuku, Tadashi, Maeda, Hitoshi, Fukagawa, Masafumi, Maruyama, Toru
• Format: Journal Article
• Language: English
• Published: MDPI 25.05.2021; MDPI AG
• Subjects: acute kidney injury; albumin fusion; chronic kidney disease; thioredoxin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22115600

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.