Systemic and sustained thioredoxin analogue prevents acute kidney injury and its-associated distant organ damage in renal ischemia reperfusion injury mice
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 an...
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| description | 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. |
| doi_str_mv | 10.1038/s41598-020-75025-5 |
| format | Article |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-75025-5</identifier><identifier>PMID: 33244034</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/154/152 ; 692/699/1585/4 ; 692/699/1785/3193 ; Acute Kidney Injury - metabolism ; Acute Kidney Injury - prevention & control ; Acute Lung Injury - drug therapy ; Acute Lung Injury - metabolism ; Animals ; Anti-inflammatory agents ; Anti-Inflammatory Agents - pharmacology ; Antioxidants - metabolism ; Apoptosis ; Apoptosis - drug effects ; Delayed-Action Preparations - pharmacology ; Disease Models, Animal ; Fusion protein ; Humanities and Social Sciences ; Inflammation ; Interleukin 6 ; Interleukin-6 - metabolism ; Ischemia ; Kidney - drug effects ; Kidney - metabolism ; Kidneys ; Leukocyte migration ; Lung - drug effects ; Lung - metabolism ; Lungs ; Macrophage migration inhibitory factor ; Macrophage Migration-Inhibitory Factors - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; multidisciplinary ; Oxidation-Reduction - drug effects ; Oxidative stress ; Oxidative Stress - drug effects ; Reactive Oxygen Species - metabolism ; Reperfusion ; Reperfusion Injury - drug therapy ; Reperfusion Injury - metabolism ; Science ; Science (multidisciplinary) ; Serum Albumin - metabolism ; Survival ; Thioredoxin ; Thioredoxins - pharmacology ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-α</subject><ispartof>Scientific reports, 2020-11, Vol.10 (1), p.20635, Article 20635</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-9187ddc4b706a51d39387af76a2a0161c3dcf3947aa654452f235a24845ef1613</citedby><cites>FETCH-LOGICAL-c474t-9187ddc4b706a51d39387af76a2a0161c3dcf3947aa654452f235a24845ef1613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691343/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691343/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33244034$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nishida, Kento</creatorcontrib><creatorcontrib>Watanabe, Hiroshi</creatorcontrib><creatorcontrib>Miyahisa, Masako</creatorcontrib><creatorcontrib>Hiramoto, Yuto</creatorcontrib><creatorcontrib>Nosaki, Hiroto</creatorcontrib><creatorcontrib>Fujimura, Rui</creatorcontrib><creatorcontrib>Maeda, Hitoshi</creatorcontrib><creatorcontrib>Otagiri, Masaki</creatorcontrib><creatorcontrib>Maruyama, Toru</creatorcontrib><title>Systemic and sustained thioredoxin analogue prevents acute kidney injury and its-associated distant organ damage in renal ischemia reperfusion injury mice</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>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.</description><subject>631/154/152</subject><subject>692/699/1585/4</subject><subject>692/699/1785/3193</subject><subject>Acute Kidney Injury - metabolism</subject><subject>Acute Kidney Injury - prevention & control</subject><subject>Acute Lung Injury - drug therapy</subject><subject>Acute Lung Injury - metabolism</subject><subject>Animals</subject><subject>Anti-inflammatory agents</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Antioxidants - metabolism</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Delayed-Action Preparations - pharmacology</subject><subject>Disease Models, Animal</subject><subject>Fusion protein</subject><subject>Humanities and Social Sciences</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishida, Kento</au><au>Watanabe, Hiroshi</au><au>Miyahisa, Masako</au><au>Hiramoto, Yuto</au><au>Nosaki, Hiroto</au><au>Fujimura, Rui</au><au>Maeda, Hitoshi</au><au>Otagiri, Masaki</au><au>Maruyama, Toru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Systemic and sustained thioredoxin analogue prevents acute kidney injury and its-associated distant organ damage in renal ischemia reperfusion injury mice</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-11-26</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>20635</spage><pages>20635-</pages><artnum>20635</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33244034</pmid><doi>10.1038/s41598-020-75025-5</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 631/154/152 692/699/1585/4 692/699/1785/3193 Acute Kidney Injury - metabolism Acute Kidney Injury - prevention & control Acute Lung Injury - drug therapy Acute Lung Injury - metabolism Animals Anti-inflammatory agents Anti-Inflammatory Agents - pharmacology Antioxidants - metabolism Apoptosis Apoptosis - drug effects Delayed-Action Preparations - pharmacology Disease Models, Animal Fusion protein Humanities and Social Sciences Inflammation Interleukin 6 Interleukin-6 - metabolism Ischemia Kidney - drug effects Kidney - metabolism Kidneys Leukocyte migration Lung - drug effects Lung - metabolism Lungs Macrophage migration inhibitory factor Macrophage Migration-Inhibitory Factors - metabolism Male Mice Mice, Inbred C57BL multidisciplinary Oxidation-Reduction - drug effects Oxidative stress Oxidative Stress - drug effects Reactive Oxygen Species - metabolism Reperfusion Reperfusion Injury - drug therapy Reperfusion Injury - metabolism Science Science (multidisciplinary) Serum Albumin - metabolism Survival Thioredoxin Thioredoxins - pharmacology Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-α |
| title | Systemic and sustained thioredoxin analogue prevents acute kidney injury and its-associated distant organ damage in renal ischemia reperfusion injury mice |
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