論文 - 詳細
| RRC ID | 88561 |
|---|---|
| 著者 | Gong Y, Zhu W, Li Y, Lu T, Tan J, He C, Yang L, Zhu Y, Gong L. |
| タイトル | Dynamic regulation of proximal tubular autophagy from injury to repair after ischemic kidney damage. |
| ジャーナル | Cell Mol Biol Lett |
| Abstract |
BACKGROUND:The role of proximal tubular autophagy in repairing kidney injury following ischemia remains unclear. METHODS:In this study, we utilized mice with conditional deletion of the Atg5 gene in proximal tubules and monitored the long-term dynamic regulation of autophagy following ischemic acute kidney injury (AKI). RESULTS:The results showed that Atg5-deficient proximal tubule epithelial cells exhibited damaged mitochondria, concentric membranes, and lysosomal accumulation 24 h after ischemia/reperfusion. However, 28 days after ischemia/reperfusion, concentric membrane bodies remained, but lysosomal accumulation was no longer observed. Notably, the absence of Atg5 in renal tubular epithelial cells impaired renal function and led to increased tubular cell proliferation and oxidative stress in the early stage of injury. However, during the repair period following AKI, Atg5 deficiency exhibited no significant difference in the expression of proliferating cell nuclear antigen (PCNA) and 4-hydoxynonenal (4HNE), suggesting that the improvement in renal fibrosis associated with Atg5 deficiency is unlikely to result from its effect on cell proliferation or reactive oxygen species levels. Additionally, Atg5 deficiency inhibits the secretion of profibrotic factor fibroblast growth factor 2 (FGF2) from the early stage of renal injury to the recovery stage of AKI, indicating that autophagy-specific regulation of FGF2 secretion is a dynamic process overlapping with other stages of injury. Furthermore, increased co-localization of ATG5 with 4HNE and FGF2 was observed in patient samples. CONCLUSION:In summary, our results suggest that the dynamic regulation of autophagy on key molecules involved in kidney injury and repair varies with the stage of kidney injury. |
| 巻・号 | 29(1) |
| ページ | 151 |
| 公開日 | 2024-12-5 |
| DOI | 10.1186/s11658-024-00663-w |
| PII | 10.1186/s11658-024-00663-w |
| PMID | 39639205 |
| PMC | PMC11619129 |
| MeSH | Acute Kidney Injury* / genetics Acute Kidney Injury* / metabolism Acute Kidney Injury* / pathology Animals Autophagy* Autophagy-Related Protein 5* / genetics Autophagy-Related Protein 5* / metabolism Cell Proliferation Epithelial Cells / metabolism Epithelial Cells / pathology Fibroblast Growth Factor 2 / genetics Fibroblast Growth Factor 2 / metabolism Kidney Tubules, Proximal* / metabolism Kidney Tubules, Proximal* / pathology Male Mice Mice, Inbred C57BL Mice, Knockout Oxidative Stress Reperfusion Injury* / genetics Reperfusion Injury* / metabolism Reperfusion Injury* / pathology |
| リソース情報 | |
| 実験動物マウス | RBRC02975 |