Upregulated DJ-1 promotes renal tubular EMT by suppressing cytoplasmic PTEN expression and Akt activation

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Updated: May 30, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Ying Yao1, Honglan Wei1, Lili Liu1

  • 1Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban
|August 9, 2011
PubMed

Insights

DJ-1 is upregulated in renal fibrosis, promoting epithelial-mesenchymal transition (EMT) by suppressing cytoplasmic PTEN expression and activating Akt. This suggests DJ-1 as a therapeutic target for fibrotic kidney disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) shows potential in treating fibrogenesis.
  • DJ-1 is a known negative regulator of PTEN in tumors, but its role in fibrosis is undetermined.
  • Understanding DJ-1 and PTEN regulation is crucial for developing antifibrotic therapies.

Purpose of the Study:

  • To investigate the expression and regulation of DJ-1 and PTEN in renal fibrosis.
  • To elucidate the role of DJ-1 in mediating epithelial-mesenchymal transition (EMT) in kidney cells.

Main Methods:

  • Induced renal fibrosis in a 5/6 subtotal nephrectomy rat model.
  • Treated human proximal tubular epithelial cells (HKC) with transforming growth factor-beta 1 (TGF-β1).
  • Utilized confocal microscopy, RT-PCR, Western blotting, and immunocytochemistry to assess protein localization, expression, and pathway activation.

Main Results:

  • TGF-β1 upregulated DJ-1 expression and downregulated PTEN expression in both HKC cells and rat kidneys.
  • TGF-β1 induced translocation of DJ-1 to cytoplasm and nucleus, and PTEN from cytoplasm to nucleus.
  • Overexpression of DJ-1 promoted EMT markers (vimentin), Akt activation, and reduced cytoplasmic PTEN, while PTEN overexpression protected against TGF-β1-induced EMT.

Conclusions:

  • DJ-1 is upregulated in renal fibrosis, playing a key role in mediating EMT.
  • DJ-1 suppresses cytoplasmic PTEN expression and promotes Akt activation, contributing to fibrogenesis.
  • Targeting DJ-1 may offer a novel therapeutic strategy for renal fibrosis.

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