Transcription Factor NFE2L1 Decreases in Glomerulonephropathies after Podocyte Damage

Cells. 2023 Aug 29;12(17):2165. doi: 10.3390/cells12172165.

Abstract

Podocyte cellular injury and detachment from glomerular capillaries constitute a critical factor contributing to kidney disease. Notably, transcription factors are instrumental in maintaining podocyte differentiation and homeostasis. This study explores the hitherto uninvestigated expression of Nuclear Factor Erythroid 2-related Factor 1 (NFE2L1) in podocytes. We evaluated the podocyte expression of NFE2L1, Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2), and NAD(P)H:quinone Oxidoreductase (NQO1) in 127 human glomerular disease biopsies using multiplexed immunofluorescence and image analysis. We found that both NFE2L1 and NQO1 expressions were significantly diminished across all observed renal diseases. Furthermore, we exposed human immortalized podocytes and ex vivo kidney slices to Puromycin Aminonucleoside (PAN) and characterized the NFE2L1 protein isoform expression. PAN treatment led to a reduction in the nuclear expression of NFE2L1 in ex vivo kidney slices and podocytes.

Keywords: NFE2L1; NQO1; glomerular disease; podocytes; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation
  • Humans
  • Kidney
  • Kidney Diseases*
  • Kidney Glomerulus
  • NAD
  • NF-E2-Related Factor 1
  • Podocytes*

Substances

  • NAD
  • NFE2L1 protein, human
  • NF-E2-Related Factor 1

Grants and funding

This work was supported by NHS Lothian. This project received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 101017453 as part of the KATY project, and from NuCana plc.