Rapamycin-induced autophagy protects proximal tubular renal cells against proteinuric damage through the transcriptional activation of the nerve growth factor receptor NGFR

Autophagy
D VizzaRenzo Bonofiglio

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 enhanc...Continue Reading

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Citations

Jun 23, 2020·Oxidative Medicine and Cellular Longevity·So-Hyun ParkChang Hwa Jung
Sep 26, 2020·Frontiers in Immunology·Siyuan ChenWenkai Ren
Sep 21, 2021·American Journal of Physiology. Renal Physiology·Yushi UchidaTakanari Kitazono

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Methods Mentioned

BETA
PCR
transfection
nuclear translocation
transmission electron microscopy
ChIP
immunoprecipitation assay
lipidation
Protein Assay
reverse transcription PCR
electrophoresis

Software Mentioned

GraphPad Prism
ImageJ
Alibaba

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