ArticleClinical and translational medicine2024
Rictor/mTORC2 signalling contributes to renal vascular endothelial-to-mesenchymal transition and renal allograft interstitial fibrosis by regulating BNIP3-mediated mitophagy.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Compensatory Mitophagy via NEDD4/HIF-1α/BNIP3 Pathway Restrains EndMT and Renal Allograft Interstitial Fibrosis Induced by TNFα.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanisms and Therapeutic Potential of Targeting Mitophagy in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Selective autophagy in kidney health and disease.Nature reviews. Nephrology · 2026Review
- Single-cell mitophagy signature-based artificial intelligence model enhances prediction of prognosis and immunotherapy response in non-small-cell lung cancer.Respiratory research · 2026Article
- Piezo1 specific deletion in endothelial cell protects the progression of pulmonary fibrosis in mice.Cell communication and signaling : CCS · 2026Article
- Ethyl acetate extract fromFrontiers in pharmacology · 2026Article
- Mitophagy and Cellular Homeostasis in Kidney Diseases: Mechanisms and Potential Therapeutics.International journal of biological sciences · 2026Review
- Dual Phosphorylation of STAT1 at Y701/S727 by TNFα Drives AIM2-Mediated PANoptosis of Renal Tubular Epithelial Cells and Fibrotic Progression in Renal Allografts.International journal of biological sciences · 2026Article
- Renal allograft interstitial fibrosis: multicellular interactions and therapeutic strategies.Frontiers in immunology · 2026Review
- Genetically prioritized mitochondrial regulators of advanced renal failure: multi-omic Mendelian randomization and biological plausibility assessment in allograft fibrosis.Frontiers in immunology · 2026Article
- Rictor/mTORC2 signaling pathway mediates Benzo[a]pyrene-induced renal injury.Scientific reports · 2025Article
- Modulation of mTOR Within Retinal Pigment Epithelium Affects Cell Viability and Mitochondrial Pathology.International journal of molecular sciences · 2025Article
- Whole transcriptome sequencing to uncover CircRNA expression patterns linked to schizophrenia pathogenesis.European journal of medical research · 2025Article
- CAV1 promotes epithelial-to-mesenchymal transition (EMT) and chronic renal allograft interstitial fibrosis by activating the ferroptosis pathway.Frontiers in immunology · 2025Article
- Single-cell RNA-seq uncovers lineage-specific regulatory alterations of fibroblasts and endothelial cells in ligamentum flavum hypertrophy.Frontiers in immunology · 2025Article
- Rictor/mTORC2 signalling contributes to renal vascular endothelial-to-mesenchymal transition and renal allograft interstitial fibrosis by regulating BNIP3-mediated mitophagy.Clinical and translational medicine · 2024Article
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12 authors.
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Abstract
backgroundRenal allograft interstitial fibrosis/tubular atrophy (IF/TA) constitutes the principal histopathological characteristic of chronic allograft dysfunction (CAD) in kidney-transplanted patients. While renal vascular endothelial-mesenchymal transition (EndMT) has been verified as an important contributing factor to IF/TA in CAD patients, its underlying mechanisms remain obscure. Through single-cell transcriptomic analysis, we identified Rictor as a potential pivotal mediator for EndMT. This investigation sought to elucidate the role of Rictor/mTORC2 signalling in the pathogenesis of renal allograft interstitial fibrosis and the associated mechanisms.
methodsThe influence of the Rictor/mTOR2 pathway on renal vascular EndMT and renal allograft fibrosis was investigated by cell experiments and Rictor depletion in renal allogeneic transplantation mice models. Subsequently, a series of assays were conducted to explore the underlying mechanisms of the enhanced mitophagy and the ameliorated EndMT resulting from Rictor knockout.
resultsOur findings revealed a significant activation of the Rictor/mTORC2 signalling in CAD patients and allogeneic kidney transplanted mice. The suppression of Rictor/mTORC2 signalling alleviated TNFα-induced EndMT in HUVECs. Moreover, Rictor knockout in endothelial cells remarkably ameliorated renal vascular EndMT and allograft interstitial fibrosis in allogeneic kidney transplanted mice. Mechanistically, Rictor knockout resulted in an augmented BNIP3-mediated mitophagy in endothelial cells. Furthermore, Rictor/mTORC2 facilitated the MARCH5-mediated degradation of BNIP3 at the K130 site through K48-linked ubiquitination, thereby regulating mitophagy activity. Subsequent experiments also demonstrated that BNIP3 knockdown nearly reversed the enhanced mitophagy and mitigated EndMT and allograft interstitial fibrosis induced by Rictor knockout.
conclusionsConsequently, our study underscores Rictor/mTORC2 signalling as a critical mediator of renal vascular EndMT and allograft interstitial fibrosis progression, exerting its impact through regulating BNIP3-mediated mitophagy. This insight unveils a potential therapeutic target for mitigating renal allograft interstitial fibrosis.
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