Influence of autophagy on acute kidney injury in a murine cecal ligation and puncture sepsis model
| Autor: | Takehiko Oami, Satoshi Sunahara, Takashi Shimazui, Chiwei Lee, Paul E. Swanson, Lisa Fujimura, Youichi Teratake, Shigeto Oda, Masahiko Hatano, Eizo Watanabe |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine lcsh:Medicine Renal function Kidney Article Andrology Sepsis Mice 03 medical and health sciences 0302 clinical medicine Autophagy Animals Medicine lcsh:Science Multidisciplinary LAMP1 business.industry lcsh:R Autophagosomes Acute kidney injury Kidney metabolism Acute Kidney Injury medicine.disease Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis embryonic structures lcsh:Q biological phenomena cell phenomena and immunity Lysosomes business Homeostasis |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The role of autophagy in the maintenance of renal homeostasis during sepsis is not well understood. We therefore aimed to determine the influence of autophagy on kidney during sepsis using a murine sepsis model, i.e. cecal ligation and puncture (CLP). In CLP treated animals, the number of autolysosomes observed by electron microscopy increased over time. The number of autophagosomes in CLP animals decreased relative sham operated controls at 24 hrs after CLP, indicating that autophagy flux is already diminishing by that time. Moreover, CLP induced an increase in LC3-II/LC3-I ratio at 6–8 hrs, demonstrated in western blots, as well as an increase in GFP-LC3 dots at 6–8 hrs and 24 hrs, using immunofluorescence and anti-LC3 and LAMP1 antibodies on tissue sections from GFP-LC3 transgenic mice. LC3-II/LC3-I ratio and the number of co-localized GFP-LC3 dots and LAMP1 signals (GFP LC3 + LAMP1 dots) in CLP mice at 24 hrs were significantly reduced compared with data obtained at 6–8 hrs. Notably, acceleration of autophagy by rapamycin resulted in improvement of renal function that was associated with improvement in the histologic severity of tubular epithelial injury in CLP treated animals. Autophagy in the kidney was significantly slowed in the kidney during the acute phase of sepsis; nonetheless, autophagy in kidney appears to play a protective role against sepsis. |
| Databáze: | OpenAIRE |
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