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Transcription factor c-Maf deletion improves streptozotocin-induced diabetic nephropathy by directly regulating Sglt2

Mitsunori Fujino1,2, Naoki Morito3, Takuto Hayashi1,4

  • 1Department of Anatomy and Embryology, Faculty of Medicine.

JCI Insight
|February 14, 2023
PubMed

Insights

The transcription factor c-Maf plays a key role in adult kidney function. Deleting c-Maf in adult mice caused kidney injury but protected against diabetic nephropathy by downregulating SGLT2 and GLUT2.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Genetics

Background:

  • The transcription factor c-Maf is crucial for embryonic kidney development.
  • Postnatal functions of c-Maf in adult kidneys are largely unknown due to embryonic lethality in c-Maf-null mice.

Purpose of the Study:

  • To investigate the role of c-Maf in adult mouse kidneys.
  • To determine the effects of c-Maf deletion on diabetic kidney conditions.

Main Methods:

  • Utilized tamoxifen-inducible c-Maf-knockout mice (c-MafΔTAM) and control littermates.
  • Administered tamoxifen (TAM) to induce knockout and streptozotocin (STZ) to induce diabetes.
  • Analyzed kidney phenotypes, gene expression (Sglt2, Glut2), and diabetic nephropathy markers.

Main Results:

  • Non-diabetic c-MafΔTAM mice developed glycosuria due to Sglt2 and Glut2 downregulation, alongside kidney injury.
  • In diabetic conditions, c-Maf deletion improved hyperglycemia, reduced albuminuria, and suppressed diabetic nephropathy.
  • The effects of c-Maf deletion mimicked Sglt2 knockout and SGLT2 inhibitor treatments.

Conclusions:

  • c-Maf plays a significant role in adult kidney physiology and pathophysiology.
  • c-Maf deficiency confers renoprotective effects in diabetic conditions.
  • c-Maf represents a potential therapeutic target for diabetic nephropathy.
Keywords:
Chronic kidney diseaseDiabetesNephrology

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