HYAL1 deficiency attenuates lipopolysaccharide-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice
Background Renal dysfunction and disruption of renal endothelial glycocalyx are two important events during septic acute kidney injury (AKI). Here, the role and mechanism of hyaluronidase 1 (HYAL1) in regulating renal injury and renal endothelial glycocalyx breakdown in septic AKI were explored for...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2023.2188966 |
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| author | Hongxia Xing Shensen Li Yongchao Fu Xin Wan Annan Zhou Feifei Cao Qing Sun Nana Hu Mengqing Ma Wenwen Li Changchun Cao |
| author_facet | Hongxia Xing Shensen Li Yongchao Fu Xin Wan Annan Zhou Feifei Cao Qing Sun Nana Hu Mengqing Ma Wenwen Li Changchun Cao |
| author_sort | Hongxia Xing |
| collection | DOAJ |
| description | Background Renal dysfunction and disruption of renal endothelial glycocalyx are two important events during septic acute kidney injury (AKI). Here, the role and mechanism of hyaluronidase 1 (HYAL1) in regulating renal injury and renal endothelial glycocalyx breakdown in septic AKI were explored for the first time.Methods BALB/c mice were injected with lipopolysaccharide (LPS, 10 mg/kg) to induce AKI. HYAL1 was blocked in vivo using lentivirus-mediated short hairpin RNA targeting HYAL1 (LV-sh-HYAL1). Biochemical assays were performed to measure the levels and concentrations of biochemical parameters associated with AKI as well as levels of inflammatory cytokines. Renal pathological lesions were determined by hematoxylin-eosin (HE) staining. Cell apoptosis in the kidney was detected using terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL) assay. Immunofluorescence and immunohistochemical (IHC) staining assays were used to examine the levels of hyaluronic acid in the kidney. The protein levels of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, endothelial glycocalyx, and autophagy-associated indicators were assessed by western blotting.Results The knockdown of HYAL1 in LPS-subjected mice by LV-sh-HYAL1 significantly reduced renal inflammation, oxidative stress, apoptosis and kidney dysfunction in AKI, as well as alleviated renal endothelial glycocalyx disruption by preventing the release of hyaluronic acid to the bloodstream. Additionally, autophagy-related protein analysis indicated that knockdown of HYAL1 significantly enhanced autophagy in LPS mice. Furthermore, the beneficial actions of HYAL1 blockade were closely associated with the AMPK/mTOR signaling.Conclusion HYAL1 deficiency attenuates LPS-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice. |
| format | Article |
| id | doaj-art-507667333bce461aa149d2a460a7a604 |
| institution | DOAJ |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-507667333bce461aa149d2a460a7a6042025-08-20T02:56:09ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492023-12-0145110.1080/0886022X.2023.2188966HYAL1 deficiency attenuates lipopolysaccharide-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in miceHongxia Xing0Shensen Li1Yongchao Fu2Xin Wan3Annan Zhou4Feifei Cao5Qing Sun6Nana Hu7Mengqing Ma8Wenwen Li9Changchun Cao10Department of Nephrology, Sir Run Hospital, Nanjing Medical University, Jiangsu, China NanjingDepartment of Nephrology, Sir Run Hospital, Nanjing Medical University, Jiangsu, China NanjingDepartment of Nephrology, Sir Run Hospital, Nanjing Medical University, Jiangsu, China NanjingDepartment of Nephrology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China NanjingDepartment of Nephrology, Sir Run Hospital, Nanjing Medical University, Jiangsu, China NanjingDepartment of Nephrology, Sir Run Hospital, Nanjing Medical University, Jiangsu, China NanjingDepartment of Nephrology, Sir Run Hospital, Nanjing Medical University, Jiangsu, China NanjingDepartment of Nephrology, Sir Run Hospital, Nanjing Medical University, Jiangsu, China NanjingDepartment of Nephrology, Sir Run Hospital, Nanjing Medical University, Jiangsu, China NanjingDepartment of Nephrology, Sir Run Hospital, Nanjing Medical University, Jiangsu, China NanjingDepartment of Nephrology, Sir Run Hospital, Nanjing Medical University, Jiangsu, China NanjingBackground Renal dysfunction and disruption of renal endothelial glycocalyx are two important events during septic acute kidney injury (AKI). Here, the role and mechanism of hyaluronidase 1 (HYAL1) in regulating renal injury and renal endothelial glycocalyx breakdown in septic AKI were explored for the first time.Methods BALB/c mice were injected with lipopolysaccharide (LPS, 10 mg/kg) to induce AKI. HYAL1 was blocked in vivo using lentivirus-mediated short hairpin RNA targeting HYAL1 (LV-sh-HYAL1). Biochemical assays were performed to measure the levels and concentrations of biochemical parameters associated with AKI as well as levels of inflammatory cytokines. Renal pathological lesions were determined by hematoxylin-eosin (HE) staining. Cell apoptosis in the kidney was detected using terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL) assay. Immunofluorescence and immunohistochemical (IHC) staining assays were used to examine the levels of hyaluronic acid in the kidney. The protein levels of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, endothelial glycocalyx, and autophagy-associated indicators were assessed by western blotting.Results The knockdown of HYAL1 in LPS-subjected mice by LV-sh-HYAL1 significantly reduced renal inflammation, oxidative stress, apoptosis and kidney dysfunction in AKI, as well as alleviated renal endothelial glycocalyx disruption by preventing the release of hyaluronic acid to the bloodstream. Additionally, autophagy-related protein analysis indicated that knockdown of HYAL1 significantly enhanced autophagy in LPS mice. Furthermore, the beneficial actions of HYAL1 blockade were closely associated with the AMPK/mTOR signaling.Conclusion HYAL1 deficiency attenuates LPS-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice.https://www.tandfonline.com/doi/10.1080/0886022X.2023.2188966HYAL1AMPK/mTOR signalingacute kidney injuryendothelial glycocalyxautophagy |
| spellingShingle | Hongxia Xing Shensen Li Yongchao Fu Xin Wan Annan Zhou Feifei Cao Qing Sun Nana Hu Mengqing Ma Wenwen Li Changchun Cao HYAL1 deficiency attenuates lipopolysaccharide-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice Renal Failure HYAL1 AMPK/mTOR signaling acute kidney injury endothelial glycocalyx autophagy |
| title | HYAL1 deficiency attenuates lipopolysaccharide-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice |
| title_full | HYAL1 deficiency attenuates lipopolysaccharide-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice |
| title_fullStr | HYAL1 deficiency attenuates lipopolysaccharide-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice |
| title_full_unstemmed | HYAL1 deficiency attenuates lipopolysaccharide-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice |
| title_short | HYAL1 deficiency attenuates lipopolysaccharide-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice |
| title_sort | hyal1 deficiency attenuates lipopolysaccharide triggered renal injury and endothelial glycocalyx breakdown in septic aki in mice |
| topic | HYAL1 AMPK/mTOR signaling acute kidney injury endothelial glycocalyx autophagy |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2023.2188966 |
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