Netrin-1 improves functional recovery through autophagy regulation by activating the AKT/mTOR signaling pathway in high-glucose-induced renal proximal tubule injury
Abstract Netrin-1, a survival factor, is highly expressed in the kidney and reported to participate in some types of acute or chronic kidney diseases. Nevertheless, the causal link beneath the effect on renal proximal tubule cells of Netrin-1 under pathological conditions in diabetic nephropathy (DN) hasn't been elucidated. Our team explored the effects of Netrin-1 on the etiopathogenesis of DN. In vitro, high blood glucose caused the downregulation of Netrin-1, which induced the stimulation of AKT/mTOR signal transmission with the elevated programmed cell death of renal proximal tubule cells and increased actin cytoskeleton derangement. The supplementation of recombinant rat Netrin-1 reversed these pathological changes and it was tightly related to the recovery of autophagy flux. In addition, those pathologic variations were abolished by transfection with a lentivirus expressing short hairpin RNA against Netrin-1 or a mTOR inhibitor in vitro. The discoveries of the present research reveal that Netrin-1 is responsible for the mediation of high glucose-triggered loss of renal proximal tubule cells by regulating their detachment and programmed cell death in vitro. The present paper facilitates our comprehension regarding the causal links of renal proximal tubule cell injury in DN and reveals that targeting Netrin-1-associated signal transduction has treatment significance for DN..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 04. Mai Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Chenxiao [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-1597367/v1 |
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| funding: |
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| PPN (Katalog-ID): |
XRA035915595 |
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| 520 | |a Abstract Netrin-1, a survival factor, is highly expressed in the kidney and reported to participate in some types of acute or chronic kidney diseases. Nevertheless, the causal link beneath the effect on renal proximal tubule cells of Netrin-1 under pathological conditions in diabetic nephropathy (DN) hasn't been elucidated. Our team explored the effects of Netrin-1 on the etiopathogenesis of DN. In vitro, high blood glucose caused the downregulation of Netrin-1, which induced the stimulation of AKT/mTOR signal transmission with the elevated programmed cell death of renal proximal tubule cells and increased actin cytoskeleton derangement. The supplementation of recombinant rat Netrin-1 reversed these pathological changes and it was tightly related to the recovery of autophagy flux. In addition, those pathologic variations were abolished by transfection with a lentivirus expressing short hairpin RNA against Netrin-1 or a mTOR inhibitor in vitro. The discoveries of the present research reveal that Netrin-1 is responsible for the mediation of high glucose-triggered loss of renal proximal tubule cells by regulating their detachment and programmed cell death in vitro. The present paper facilitates our comprehension regarding the causal links of renal proximal tubule cell injury in DN and reveals that targeting Netrin-1-associated signal transduction has treatment significance for DN. | ||
| 700 | 1 | |a Wu, Mian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Aijie |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xingna |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jiaqi |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Honghong |e verfasserin |4 aut | |
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