Nafamostat Mesylate Regulates Glycosylation to Alleviate Aristolochic Acid Induced Kidney Injury
Acute kidney injury (AKI) is a condition with a poor prognosis, exacerbated by the lack of effective therapeutic options and inadequately understood underlying mechanisms. Glycosylation, a post-translational modification of proteins, is essential for maintaining protein stability and function, and i...
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MDPI AG
2025-03-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/17/3/145 |
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| author | Pei Xie Huijun Liu Xingli Huo Junlong Chen Yu Li Yu Huang Zongning Yin |
| author_facet | Pei Xie Huijun Liu Xingli Huo Junlong Chen Yu Li Yu Huang Zongning Yin |
| author_sort | Pei Xie |
| collection | DOAJ |
| description | Acute kidney injury (AKI) is a condition with a poor prognosis, exacerbated by the lack of effective therapeutic options and inadequately understood underlying mechanisms. Glycosylation, a post-translational modification of proteins, is essential for maintaining protein stability and function, and its dysregulation leads to protein misfolding and amyloid aggregation. Glycosylation dynamics are implicated in several pathologies, including inflammation, cancer, and AKI, highlighting the therapeutic potential of regulating glycosylation and preventing aggregation in AKI treatment. This study investigates the effect of nafamostat mesylate (NM) on protein glycosylation and amyloid aggregation in vivo. Using optical spectroscopy and other analytical techniques, we demonstrate that NM restores glycosylation levels and inhibits protein aggregation in aristolochic-acid-induced acute kidney injury. The mechanism likely involves enzymatic modulation that corrects hypoglycosylation and prevents amyloid aggregation, promoting proper protein folding and enhancing its stability. These findings suggest that NM may provide a novel therapeutic strategy for AKI and other glycosylation-related diseases, underscoring the potential for early intervention and treatment of these conditions. |
| format | Article |
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| institution | Kabale University |
| issn | 2072-6651 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj-art-ff4e5635ad1d4636b2918ec55befdf6f2025-08-20T03:44:01ZengMDPI AGToxins2072-66512025-03-0117314510.3390/toxins17030145Nafamostat Mesylate Regulates Glycosylation to Alleviate Aristolochic Acid Induced Kidney InjuryPei Xie0Huijun Liu1Xingli Huo2Junlong Chen3Yu Li4Yu Huang5Zongning Yin6Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaHaisco Pharmaceutical Group Co., Ltd., Chengdu 611130, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaAcute kidney injury (AKI) is a condition with a poor prognosis, exacerbated by the lack of effective therapeutic options and inadequately understood underlying mechanisms. Glycosylation, a post-translational modification of proteins, is essential for maintaining protein stability and function, and its dysregulation leads to protein misfolding and amyloid aggregation. Glycosylation dynamics are implicated in several pathologies, including inflammation, cancer, and AKI, highlighting the therapeutic potential of regulating glycosylation and preventing aggregation in AKI treatment. This study investigates the effect of nafamostat mesylate (NM) on protein glycosylation and amyloid aggregation in vivo. Using optical spectroscopy and other analytical techniques, we demonstrate that NM restores glycosylation levels and inhibits protein aggregation in aristolochic-acid-induced acute kidney injury. The mechanism likely involves enzymatic modulation that corrects hypoglycosylation and prevents amyloid aggregation, promoting proper protein folding and enhancing its stability. These findings suggest that NM may provide a novel therapeutic strategy for AKI and other glycosylation-related diseases, underscoring the potential for early intervention and treatment of these conditions.https://www.mdpi.com/2072-6651/17/3/145nafamostat mesylateacute kidney injuryglycosylationprotein foldingaristolochic acid |
| spellingShingle | Pei Xie Huijun Liu Xingli Huo Junlong Chen Yu Li Yu Huang Zongning Yin Nafamostat Mesylate Regulates Glycosylation to Alleviate Aristolochic Acid Induced Kidney Injury Toxins nafamostat mesylate acute kidney injury glycosylation protein folding aristolochic acid |
| title | Nafamostat Mesylate Regulates Glycosylation to Alleviate Aristolochic Acid Induced Kidney Injury |
| title_full | Nafamostat Mesylate Regulates Glycosylation to Alleviate Aristolochic Acid Induced Kidney Injury |
| title_fullStr | Nafamostat Mesylate Regulates Glycosylation to Alleviate Aristolochic Acid Induced Kidney Injury |
| title_full_unstemmed | Nafamostat Mesylate Regulates Glycosylation to Alleviate Aristolochic Acid Induced Kidney Injury |
| title_short | Nafamostat Mesylate Regulates Glycosylation to Alleviate Aristolochic Acid Induced Kidney Injury |
| title_sort | nafamostat mesylate regulates glycosylation to alleviate aristolochic acid induced kidney injury |
| topic | nafamostat mesylate acute kidney injury glycosylation protein folding aristolochic acid |
| url | https://www.mdpi.com/2072-6651/17/3/145 |
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