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Podocyte apoptosis in diabetic nephropathy by BASP1 activation of the p53 pathway via WT1

Yingying Zhang1, Chengxian Xu1, Qing Ye1

  • 1Department of Nephrology, The Children Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China.

Acta Physiologica (Oxford, England)
|February 22, 2021
PubMed
Abstract

Insights

Brain acid-soluble protein (BASP1) is elevated in diabetic nephropathy (DN). Deleting BASP1 in podocytes protects kidneys. BASP1 activates the p53 pathway, inducing podocyte apoptosis in DN.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Diabetic nephropathy (DN) is a major cause of end-stage renal disease.
  • Brain acid-soluble protein (BASP1) is upregulated in podocytes in kidney dysfunction models.

Purpose of the Study:

  • To investigate the role of BASP1 in podocytes during diabetic nephropathy.
  • To elucidate the molecular mechanisms by which BASP1 affects podocyte injury and apoptosis.

Main Methods:

  • BASP1 expression analysis in human DN kidneys and mouse models.
  • Generation and study of podocyte-specific BASP1 knockout mice (Pod-BASP1-KO).
  • In vitro studies using mouse podocyte cell line (MPC5) with BASP1 knockdown/overexpression to assess apoptosis and signaling pathways.

Main Results:

  • BASP1 expression is increased in DN patients and mouse models.
  • Podocyte-specific deletion of BASP1 ameliorates podocyte injury and protects against DN.
  • BASP1 promotes podocyte apoptosis and actin cytoskeleton rearrangement.
  • BASP1 co-represses with WT1 to activate the p53 pathway in high glucose-treated podocytes.

Conclusions:

  • BASP1 plays a critical role in promoting podocyte apoptosis in diabetic nephropathy.
  • BASP1 activates the p53 pathway via WT1 modulation, leading to podocyte injury in DN.
  • Targeting BASP1 may offer a therapeutic strategy for diabetic nephropathy.
Keywords:
BASP1apoptosisdiabetic nephropathyp53podocyte

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