ArticleAutophagy2018
Rapamycin-induced autophagy protects proximal tubular renal cells against proteinuric damage through the transcriptional activation of the nerve growth factor receptor NGFR.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Crotonylome profiling identifies MLKL crotonylation in lupus nephritis associated with RAB1A-mTOR signalling and autophagy changes in tubular epithelial cells.Lupus science & medicine · 2026Article
- Targeted inhibition of RGS19 alleviates renal fibrosis by restoring autophagy and modulating immune cell infiltration.Journal of nanobiotechnology · 2026Article
- Small molecule modulation of p75Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- The novelAutophagy · 2024Article
- Tubulointerstitial injury in proteinuric chronic kidney diseases.Frontiers in medicine · 2024Review
- Review
- RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer.Scientific reports · 2022Article
- Resveratrol Induces Autophagy and Apoptosis in Non-Small-Cell Lung Cancer Cells by Activating the NGFR-AMPK-mTOR Pathway.Nutrients · 2022Article
- Evaluation of PGP 9.5, NGFR, TGFβ1, FGFR1, MMP-2, AT2R2, SHH, and TUNEL in Primary Obstructive Megaureter Tissue.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Article
- The Role of Autophagy in Lamellar Body Formation and Surfactant Production in Type 2 Alveolar Epithelial Cells.International journal of biological sciences · 2022Article
- Rapamycin inhibits LOC102553434-mediated pyroptosis to improve lung injury induced by limb ischemia-reperfusion.3 Biotech · 2021Article
- A novel palmitic acid hydroxy stearic acid (5-PAHSA) plays a neuroprotective role by inhibiting phosphorylation of the m-TOR-ULK1 pathway and regulating autophagy.CNS neuroscience & therapeutics · 2021Article
- The Active Compounds and Therapeutic Target ofFrontiers in medicine · 2021Review
- Promoting effect of rapamycin on osteogenic differentiation of maxillary sinus membrane stem cells.PeerJ · 2021Article
- Lysosomal dysfunction-induced autophagic stress in diabetic kidney disease.Journal of cellular and molecular medicine · 2020Review
- Inhibition of miR-450b-5p ameliorates hepatic ischemia/reperfusion injury via targeting CRYAB.Cell death & disease · 2020Article
- AMPK/mTOR Signaling in Autophagy Regulation During Cisplatin-Induced Acute Kidney Injury.Frontiers in physiology · 2020Review
- Clinical efficacy and safety of sirolimus in systemic lupus erythematosus: a real-world study and meta-analysis.Therapeutic advances in musculoskeletal disease · 2020Article
- Serine Supports IL-1β Production in Macrophages Through mTOR Signaling.Frontiers in immunology · 2020Article
- Autophagy Functions to Prevent Methylglyoxal-Induced Apoptosis in HK-2 Cells.Oxidative medicine and cellular longevity · 2020Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Experimental evidence demonstrated that macroautophagy/autophagy exerts a crucial role in maintain renal cellular homeostasis and represents a protective mechanism against renal injuries. Interestingly, it has been demonstrated that in the human proximal tubular renal cell line, HK-2, the MTOR inhibitor rapamycin enhanced autophagy and mitigated the apoptosis damage induced by urinary protein overload. However, the underlying molecular mechanism has not yet been elucidated. In our study we demonstrated, for the first time, that in HK-2 cells, the exposure to low doses of rapamycin transactivated the NGFR promoter, leading to autophagic activation. Indeed, we observed that in HK-2 cells silenced for the NGFR gene, the rapamycin-induced autophagic process was prevented, as the upregulation of the proautophagic markers, BECN1, as well as LC3-II, and the autophagic vacuoles evaluated by transmission electron microscopy, were not found. Concomitantly, using a series of deletion constructs of the NGFR promoter we found that the EGR1 transcription factor was responsible for the rapamycin-mediated transactivation of the NGFR promoter. Finally, our results provided evidence that the cotreatment with rapamycin plus albumin further enhanced autophagy via NGFR activation, reducing the proapoptotic events promoted by albumin alone. This effect was prevented in HK-2 cells silenced for the NGFR gene or pretreated with the MTOR activator, MHY1485. Taken together, our results describe a novel molecular mechanism by which rapamycin-induced autophagy, mitigates the tubular renal damage caused by proteinuria, suggesting that the use of low doses of rapamycin could represent a new therapeutic strategy to counteract the tubule-interstitial injury observed in patients affected by proteinuric nephropathies, avoiding the side effects of high doses of rapamycin.
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