Transcription factor MafB in podocytes protects against the development of focal segmental glomerulosclerosis

Kidney Int. 2020 Aug;98(2):391-403. doi: 10.1016/j.kint.2020.02.038. Epub 2020 Apr 28.

Abstract

Focal segmental glomerulosclerosis (FSGS) is a common cause of steroid-resistant nephrotic syndrome. Spontaneous remission of FSGS is rare and steroid-resistant FSGS frequently progresses to renal failure. Many inheritable forms of FSGS have been described, caused by mutations in proteins that are important for podocyte function. Here, we show that a basic leucine zipper transcription factor, MafB, protects against FSGS. MAFB expression was found to be decreased in the podocytes of patients with FSGS. Moreover, conditional podocyte-specific MafB-knockout mice developed FSGS with massive proteinuria accompanied by depletion of the slit diaphragm-related proteins (Nphs1 and Magi2), and the podocyte-specific transcription factor Tcf21. These findings indicate that MafB plays a crucial role in the pathogenesis of FSGS. Consistent with this, adriamycin-induced FSGS and attendant proteinuria were ameliorated by MafB overexpression in the podocytes of MafB podocyte-specific transgenic mice. Thus, MafB could be a new therapeutic target for FSGS.

Keywords: MafB; focal segmental glomerulosclerosis; podocyte; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Glomerulosclerosis, Focal Segmental* / genetics
  • Humans
  • MafB Transcription Factor / genetics
  • Mice
  • Mice, Transgenic
  • Nephrotic Syndrome* / genetics
  • Podocytes*
  • Proteinuria / genetics
  • Proteinuria / prevention & control

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • MAFB protein, human
  • MafB Transcription Factor
  • Mafb protein, mouse
  • TCF21 protein, human