Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury
The full-length receptor for advanced glycation end products (RAGE) is a multiligand pattern recognition receptor. High-mobility group box 1 (HMGB1) is a RAGE ligand of damage-associated molecular patterns that elicits inflammatory reactions. The shedded isoform of RAGE and endogenous secretory RAGE...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2022-01-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/11/1/bio058852 |
| _version_ | 1818141659252129792 |
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| author | Taro Miyagawa Yasunori Iwata Megumi Oshima Hisayuki Ogura Koichi Sato Shiori Nakagawa Yuta Yamamura Yasutaka Kamikawa Taito Miyake Shinji Kitajima Tadashi Toyama Akinori Hara Norihiko Sakai Miho Shimizu Kengo Furuichi Seiichi Munesue Yasuhiko Yamamoto Shuichi Kaneko Takashi Wada |
| author_facet | Taro Miyagawa Yasunori Iwata Megumi Oshima Hisayuki Ogura Koichi Sato Shiori Nakagawa Yuta Yamamura Yasutaka Kamikawa Taito Miyake Shinji Kitajima Tadashi Toyama Akinori Hara Norihiko Sakai Miho Shimizu Kengo Furuichi Seiichi Munesue Yasuhiko Yamamoto Shuichi Kaneko Takashi Wada |
| author_sort | Taro Miyagawa |
| collection | DOAJ |
| description | The full-length receptor for advanced glycation end products (RAGE) is a multiligand pattern recognition receptor. High-mobility group box 1 (HMGB1) is a RAGE ligand of damage-associated molecular patterns that elicits inflammatory reactions. The shedded isoform of RAGE and endogenous secretory RAGE (esRAGE), a splice variant, are soluble isoforms (sRAGE) that act as organ-protective decoys. However, the pathophysiologic roles of RAGE/sRAGE in acute kidney injury (AKI) remain unclear. We found that AKI was more severe, with enhanced renal tubular damage, macrophage infiltration, and fibrosis, in mice lacking both RAGE and sRAGE than in wild-type (WT) control mice. Using murine tubular epithelial cells (TECs), we demonstrated that hypoxia upregulated messenger RNA (mRNA) expression of HMGB1 and tumor necrosis factor α (TNF-α), whereas RAGE and esRAGE expressions were paradoxically decreased. Moreover, the addition of recombinant sRAGE canceled hypoxia-induced inflammation and promoted cell viability in cultured TECs. sRAGE administration prevented renal tubular damage in models of ischemia/reperfusion-induced AKI and of anti-glomerular basement membrane (anti-GBM) glomerulonephritis. These results suggest that sRAGE is a novel therapeutic option for AKI. |
| first_indexed | 2024-12-11T11:03:23Z |
| format | Article |
| id | doaj.art-176dc0b309ca48d6afb43826266f8093 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-11T11:03:23Z |
| publishDate | 2022-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-176dc0b309ca48d6afb43826266f80932022-12-22T01:09:47ZengThe Company of BiologistsBiology Open2046-63902022-01-0111110.1242/bio.058852058852Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injuryTaro Miyagawa0Yasunori Iwata1Megumi Oshima2Hisayuki Ogura3Koichi Sato4Shiori Nakagawa5Yuta Yamamura6Yasutaka Kamikawa7Taito Miyake8Shinji Kitajima9Tadashi Toyama10Akinori Hara11Norihiko Sakai12Miho Shimizu13Kengo Furuichi14Seiichi Munesue15Yasuhiko Yamamoto16Shuichi Kaneko17Takashi Wada18 Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa 920-0293, Japan Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of System Biology, Institute of Medical Pharmaceutical and Health Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan The full-length receptor for advanced glycation end products (RAGE) is a multiligand pattern recognition receptor. High-mobility group box 1 (HMGB1) is a RAGE ligand of damage-associated molecular patterns that elicits inflammatory reactions. The shedded isoform of RAGE and endogenous secretory RAGE (esRAGE), a splice variant, are soluble isoforms (sRAGE) that act as organ-protective decoys. However, the pathophysiologic roles of RAGE/sRAGE in acute kidney injury (AKI) remain unclear. We found that AKI was more severe, with enhanced renal tubular damage, macrophage infiltration, and fibrosis, in mice lacking both RAGE and sRAGE than in wild-type (WT) control mice. Using murine tubular epithelial cells (TECs), we demonstrated that hypoxia upregulated messenger RNA (mRNA) expression of HMGB1 and tumor necrosis factor α (TNF-α), whereas RAGE and esRAGE expressions were paradoxically decreased. Moreover, the addition of recombinant sRAGE canceled hypoxia-induced inflammation and promoted cell viability in cultured TECs. sRAGE administration prevented renal tubular damage in models of ischemia/reperfusion-induced AKI and of anti-glomerular basement membrane (anti-GBM) glomerulonephritis. These results suggest that sRAGE is a novel therapeutic option for AKI.http://bio.biologists.org/content/11/1/bio058852receptor for advanced glycation end products (rage)soluble receptor for advanced glycation end products (srage)ischemia and reperfusionacute kidney injuryhigh-mobility group box 1 (hmgb1) |
| spellingShingle | Taro Miyagawa Yasunori Iwata Megumi Oshima Hisayuki Ogura Koichi Sato Shiori Nakagawa Yuta Yamamura Yasutaka Kamikawa Taito Miyake Shinji Kitajima Tadashi Toyama Akinori Hara Norihiko Sakai Miho Shimizu Kengo Furuichi Seiichi Munesue Yasuhiko Yamamoto Shuichi Kaneko Takashi Wada Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury Biology Open receptor for advanced glycation end products (rage) soluble receptor for advanced glycation end products (srage) ischemia and reperfusion acute kidney injury high-mobility group box 1 (hmgb1) |
| title | Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury |
| title_full | Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury |
| title_fullStr | Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury |
| title_full_unstemmed | Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury |
| title_short | Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury |
| title_sort | soluble receptor for advanced glycation end products protects from ischemia and reperfusion induced acute kidney injury |
| topic | receptor for advanced glycation end products (rage) soluble receptor for advanced glycation end products (srage) ischemia and reperfusion acute kidney injury high-mobility group box 1 (hmgb1) |
| url | http://bio.biologists.org/content/11/1/bio058852 |
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