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Scientific Reportsに論文が受理されました。（AKIが誘発する多臓器障害に対する血中滞留型チオレドキシンの有用性）

2020/11/30


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Systemic and sustained thioredoxin analogue prevents acute kidney injury and its-associated distant organ damage in renal ischemia reperfusion injury mice.
Nishida K, Watanabe H, Miyahisa M, Hiramoto Y, Nosaki H, Fujimura R, Maeda H, Otagiri M, Maruyama T.
Sci Rep. 2020 Nov 26;10(1):20635. doi: 10.1038/s41598-020-75025-5.

Systemic and sustained thioredoxin analogue prevents acute kidney injury and its-associated distant organ damage in renal ischemia reperfusion injury mice

Nishida K, Watanabe H, Miyahisa M, Hiramoto Y, Nosaki H, Fujimura R, Maeda H, Otagiri M,Maruyama T.Sci Rep. 2020 Nov 26;10(1):20635. doi:10.1038/s41598-020-75025-5.
Abstract
 The mortality of patients with acute kidney injury (AKI) remains high due to AKI associated-lung injury. An effective strategy for preventing both AKI and AKI-associated lung injury is urgently needed. Thioredoxin-1 (Trx) is a redox-active protein that possesses anti-oxidative, anti-apoptotic and anti-inflammatory properties including modulation of macrophage migration inhibitory factor (MIF), but its short half-life limits its clinical application. Therefore, we examined the preventive effect of a long-acting Trx, which is a fusion protein of albumin and Trx (HSA-Trx), against AKI and AKI-associated lung injury. Recombinant HSA-Trx was expressed using a Pichia expression system. AKI-induced lung injury mice were generated by bilateral renal ischemia reperfusion injury (IRI). HSA-Trx administration attenuated renal IRI and its-associated lung injury. Both renal and pulmonary oxidative stress were suppressed by HSA-Trx. Moreover, HSA-Trx inhibited elevations of plasma IL-6 and TNF-α level, and suppressed IL-6-CXCL1/2-mediated neutrophil infiltration into lung and TNF-α-mediated pulmonary apoptosis. Additionally, HSA-Trx suppressed renal IRI-induced MIF expression in kidney and lung. Administration of HSA-Trx resulted in a significant increase in the survival rate of renal IRI mice. Collectively, HSA-Trx could have therapeutic utility in preventing both AKI and AKI-associated lung injury as a consequence of its systemic and sustained multiple biological action.