Alginate oligosaccharide prevents renal ischemia-reperfusion injury in rats via MRC1-mediated pathway.
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Acta pharmacologica Sinica
2025
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| author | Liang, Bai-En Long, Luo-Sha Wu, Xin-Yan Huang, Mei-Ying Lai, Ying Yuan, Xi Wang, Ming-Hui Li, Meng Zheng, Qi-Qi Zhang, Hai-Ling Chen, Man-Chun Liu, Zhen-de Geng, Xin Lyu, Qian-Qian Wang, Wei-Dong Liu, Qing-Hua Liu, Wei-Zhi Li, Chun-Ling |
| author_facet | Liang, Bai-En Long, Luo-Sha Wu, Xin-Yan Huang, Mei-Ying Lai, Ying Yuan, Xi Wang, Ming-Hui Li, Meng Zheng, Qi-Qi Zhang, Hai-Ling Chen, Man-Chun Liu, Zhen-de Geng, Xin Lyu, Qian-Qian Wang, Wei-Dong Liu, Qing-Hua Liu, Wei-Zhi Li, Chun-Ling Liang, Bai-En Long, Luo-Sha Wu, Xin-Yan Huang, Mei-Ying Lai, Ying Yuan, Xi Wang, Ming-Hui Li, Meng Zheng, Qi-Qi Zhang, Hai-Ling Chen, Man-Chun Liu, Zhen-de Geng, Xin Lyu, Qian-Qian Wang, Wei-Dong Liu, Qing-Hua Liu, Wei-Zhi Li, Chun-Ling |
| collection | PubMed - marine biology |
| contents | Alginate oligosaccharide prevents renal ischemia-reperfusion injury in rats via MRC1-mediated pathway. Liang, Bai-En Long, Luo-Sha Wu, Xin-Yan Huang, Mei-Ying Lai, Ying Yuan, Xi Wang, Ming-Hui Li, Meng Zheng, Qi-Qi Zhang, Hai-Ling Chen, Man-Chun Liu, Zhen-de Geng, Xin Lyu, Qian-Qian Wang, Wei-Dong Liu, Qing-Hua Liu, Wei-Zhi Li, Chun-Ling Animals Reperfusion Injury Male Alginates Oligosaccharides Rats, Sprague-Dawley Signal Transduction Acute Kidney Injury Kidney Humans Rats Apoptosis Cell Line Acute kidney injury (AKI) is a clinical syndrome that is defined as a sudden decline in renal function and characterized by inflammation and tubular injury. Alginate oligosaccharide (AOSC), a natural product obtained from alginate by acidolysis and hydrolysis, shows activities of antioxidant, immunomodulation, and anti-inflammation. In this study, we investigated the potential of AOSC in the treatment of AKI. Renal ischemia-reperfusion (I/R) was induced in male rats by clipping both the renal artery and vein for 45 min followed by reperfusion for 24 h. The rats were treated with AOSC (100 mg/kg, i.g.) before surgery. At the end of the experiments, both kidneys were collected for protein, mRNA measurement, or histological analysis. We showed that AOSC pretreatment significantly improved glomerular and tubular function in the kidney of I/R rats. AOSC markedly inhibited I/R-induced activation of TLR4/MyD88/NF-κB/IL-1β inflammatory signaling and prevented apoptosis in the kidney. In HK2 cells subjected to hypoxia/reoxygenation (H/R) stimulation, AOSC (250-1000 μg/ml) dose-dependently prevented pro-inflammatory responses and cell apoptosis. Transcriptomic analysis revealed that I/R increased the expression levels of mannose receptor type C1 (MRC1) in the kidney, which was markedly inhibited by AOSC. Molecular docking showed that AOSC interacted with E725, N727, E733, T743, S745, and N747 of MRC1 through hydrogen bonds. MRC1 gene knockout significantly improved renal function and attenuated I/R-induced kidney inflammation and apoptosis in mice. In line with this, AOSC failed to prevent I/R-induced kidney injury in MRC1 gene knockout mice. UPLC analysis showed that the protection of AOSC in HK2 cells subjected to H/R was likely attributed to MRC1-mediated intracellular endocytosis. In conclusion, AOSC prevents I/R-induced AKI, which is at least partially mediated by MRC1. |
| format | Artículo científico |
| id | pubmed_40263568 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Acta pharmacologica Sinica |
| record_format | pubmed |
| spellingShingle | Alginate oligosaccharide prevents renal ischemia-reperfusion injury in rats via MRC1-mediated pathway. Liang, Bai-En Long, Luo-Sha Wu, Xin-Yan Huang, Mei-Ying Lai, Ying Yuan, Xi Wang, Ming-Hui Li, Meng Zheng, Qi-Qi Zhang, Hai-Ling Chen, Man-Chun Liu, Zhen-de Geng, Xin Lyu, Qian-Qian Wang, Wei-Dong Liu, Qing-Hua Liu, Wei-Zhi Li, Chun-Ling Animals Reperfusion Injury Male Alginates Oligosaccharides Rats, Sprague-Dawley Signal Transduction Acute Kidney Injury Kidney Humans Rats Apoptosis Cell Line Alginate oligosaccharide prevents renal ischemia-reperfusion injury in rats via MRC1-mediated pathway. Liang, Bai-En Long, Luo-Sha Wu, Xin-Yan Huang, Mei-Ying Lai, Ying Yuan, Xi Wang, Ming-Hui Li, Meng Zheng, Qi-Qi Zhang, Hai-Ling Chen, Man-Chun Liu, Zhen-de Geng, Xin Lyu, Qian-Qian Wang, Wei-Dong Liu, Qing-Hua Liu, Wei-Zhi Li, Chun-Ling Animals Reperfusion Injury Male Alginates Oligosaccharides Rats, Sprague-Dawley Signal Transduction Acute Kidney Injury Kidney Humans Rats Apoptosis Cell Line Acute kidney injury (AKI) is a clinical syndrome that is defined as a sudden decline in renal function and characterized by inflammation and tubular injury. Alginate oligosaccharide (AOSC), a natural product obtained from alginate by acidolysis and hydrolysis, shows activities of antioxidant, immunomodulation, and anti-inflammation. In this study, we investigated the potential of AOSC in the treatment of AKI. Renal ischemia-reperfusion (I/R) was induced in male rats by clipping both the renal artery and vein for 45 min followed by reperfusion for 24 h. The rats were treated with AOSC (100 mg/kg, i.g.) before surgery. At the end of the experiments, both kidneys were collected for protein, mRNA measurement, or histological analysis. We showed that AOSC pretreatment significantly improved glomerular and tubular function in the kidney of I/R rats. AOSC markedly inhibited I/R-induced activation of TLR4/MyD88/NF-κB/IL-1β inflammatory signaling and prevented apoptosis in the kidney. In HK2 cells subjected to hypoxia/reoxygenation (H/R) stimulation, AOSC (250-1000 μg/ml) dose-dependently prevented pro-inflammatory responses and cell apoptosis. Transcriptomic analysis revealed that I/R increased the expression levels of mannose receptor type C1 (MRC1) in the kidney, which was markedly inhibited by AOSC. Molecular docking showed that AOSC interacted with E725, N727, E733, T743, S745, and N747 of MRC1 through hydrogen bonds. MRC1 gene knockout significantly improved renal function and attenuated I/R-induced kidney inflammation and apoptosis in mice. In line with this, AOSC failed to prevent I/R-induced kidney injury in MRC1 gene knockout mice. UPLC analysis showed that the protection of AOSC in HK2 cells subjected to H/R was likely attributed to MRC1-mediated intracellular endocytosis. In conclusion, AOSC prevents I/R-induced AKI, which is at least partially mediated by MRC1. |
| title | Alginate oligosaccharide prevents renal ischemia-reperfusion injury in rats via MRC1-mediated pathway. |
| topic | Animals Reperfusion Injury Male Alginates Oligosaccharides Rats, Sprague-Dawley Signal Transduction Acute Kidney Injury Kidney Humans Rats Apoptosis Cell Line |
| url | https://pubmed.ncbi.nlm.nih.gov/40263568/ |