An acute phase protein α1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action
Abstract The molecular mechanism for acute kidney injury (AKI) and its progression to chronic kidney disease (CKD) continues to be unclear. In this study, we investigated the pathophysiological role of the acute phase protein α1-acid glycoprotein (AGP) in AKI and its progression to CKD using AGP KO...
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Nature Portfolio
2021
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oai:doaj.org-article:39863770c8144052b17dfd1f72939b0f2021-12-02T18:02:48ZAn acute phase protein α1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action10.1038/s41598-021-87217-82045-2322https://doaj.org/article/39863770c8144052b17dfd1f72939b0f2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87217-8https://doaj.org/toc/2045-2322Abstract The molecular mechanism for acute kidney injury (AKI) and its progression to chronic kidney disease (CKD) continues to be unclear. In this study, we investigated the pathophysiological role of the acute phase protein α1-acid glycoprotein (AGP) in AKI and its progression to CKD using AGP KO mice. Plasma AGP levels in WT mice were increased by about 3.5-fold on day 1–2 after renal ischemia–reperfusion (IR), and these values then gradually decreased to the level before renal IR on day 7–14. On day 1 after renal IR, the AGP KO showed higher renal dysfunction, tubular injury and renal inflammation as compared with WT. On day 14, renal function, tubular injury and renal inflammation in WT had recovered, but the recovery was delayed, and renal fibrosis continued to progress in AGP KO. These results obtained from AGP KO were rescued by the administration of human-derived AGP (hAGP) simultaneously with renal IR. In vitro experiments using RAW264.7 cells showed hAGP treatment suppressed the LPS-induced macrophage inflammatory response. These data suggest that endogenously induced AGP in early renal IR functions as a renoprotective molecule via its anti-inflammatory action. Thus, AGP represents a potential target molecule for therapeutic development in AKI and its progression CKD.Hiroshi WatanabeRui FujimuraYuto HiramotoRyota MurataKento NishidaJing BiTadashi ImafukuHisakazu KomoriHitoshi MaedaAyumi MukunokiToru TakeoNaomi NakagataMotoko TanakaKazutaka MatsushitaMasafumi FukagawaToru MaruyamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
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Medicine R Science Q Hiroshi Watanabe Rui Fujimura Yuto Hiramoto Ryota Murata Kento Nishida Jing Bi Tadashi Imafuku Hisakazu Komori Hitoshi Maeda Ayumi Mukunoki Toru Takeo Naomi Nakagata Motoko Tanaka Kazutaka Matsushita Masafumi Fukagawa Toru Maruyama An acute phase protein α1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action |
| description |
Abstract The molecular mechanism for acute kidney injury (AKI) and its progression to chronic kidney disease (CKD) continues to be unclear. In this study, we investigated the pathophysiological role of the acute phase protein α1-acid glycoprotein (AGP) in AKI and its progression to CKD using AGP KO mice. Plasma AGP levels in WT mice were increased by about 3.5-fold on day 1–2 after renal ischemia–reperfusion (IR), and these values then gradually decreased to the level before renal IR on day 7–14. On day 1 after renal IR, the AGP KO showed higher renal dysfunction, tubular injury and renal inflammation as compared with WT. On day 14, renal function, tubular injury and renal inflammation in WT had recovered, but the recovery was delayed, and renal fibrosis continued to progress in AGP KO. These results obtained from AGP KO were rescued by the administration of human-derived AGP (hAGP) simultaneously with renal IR. In vitro experiments using RAW264.7 cells showed hAGP treatment suppressed the LPS-induced macrophage inflammatory response. These data suggest that endogenously induced AGP in early renal IR functions as a renoprotective molecule via its anti-inflammatory action. Thus, AGP represents a potential target molecule for therapeutic development in AKI and its progression CKD. |
| format |
article |
| author |
Hiroshi Watanabe Rui Fujimura Yuto Hiramoto Ryota Murata Kento Nishida Jing Bi Tadashi Imafuku Hisakazu Komori Hitoshi Maeda Ayumi Mukunoki Toru Takeo Naomi Nakagata Motoko Tanaka Kazutaka Matsushita Masafumi Fukagawa Toru Maruyama |
| author_facet |
Hiroshi Watanabe Rui Fujimura Yuto Hiramoto Ryota Murata Kento Nishida Jing Bi Tadashi Imafuku Hisakazu Komori Hitoshi Maeda Ayumi Mukunoki Toru Takeo Naomi Nakagata Motoko Tanaka Kazutaka Matsushita Masafumi Fukagawa Toru Maruyama |
| author_sort |
Hiroshi Watanabe |
| title |
An acute phase protein α1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action |
| title_short |
An acute phase protein α1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action |
| title_full |
An acute phase protein α1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action |
| title_fullStr |
An acute phase protein α1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action |
| title_full_unstemmed |
An acute phase protein α1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action |
| title_sort |
acute phase protein α1-acid glycoprotein mitigates aki and its progression to ckd through its anti-inflammatory action |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/39863770c8144052b17dfd1f72939b0f |
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