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A negative feedback loop between JNK-associated leucine zipper protein and TGF-β1 regulates kidney fibrosis

Qi Yan1,2, Kai Zhu1, Lu Zhang1,3

  • 1Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.

Communications Biology
|June 7, 2020
PubMed

Insights

JNK-associated leucine zipper protein (JLP) acts as an antifibrotic factor in kidneys. Lower JLP levels worsen renal fibrosis, while increased JLP protects against kidney damage by regulating TGF-β1.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Renal fibrosis, a common pathway to organ failure, is driven by complex profibrotic and antifibrotic mechanisms.
  • Identifying novel antifibrotic factors is crucial for developing therapeutic strategies against kidney disease.

Purpose of the Study:

  • To investigate the role of JNK-associated leucine zipper protein (JLP) as a potential endogenous antifibrotic factor in the kidney.
  • To elucidate the molecular mechanisms by which JLP influences renal fibrosis.

Main Methods:

  • Utilized unilateral ureteral obstruction (UUO) mouse models to study renal fibrosis.
  • Generated TECs-specific transgenic Jlp mice to assess JLP's protective effects.
  • Analyzed JLP expression in normal and fibrotic kidneys.
  • Investigated the regulation of TGF-β1, autophagy, ECM production, EMT, apoptosis, and cell cycle arrest.

Main Results:

  • JLP expression was downregulated in fibrotic kidneys.
  • Jlp deficiency exacerbated renal fibrosis in UUO mice.
  • TECs-specific transgenic Jlp mice exhibited resistance to renal fibrosis.
  • JLP negatively regulated TGF-β1 expression, autophagy, ECM production, EMT, apoptosis, and cell cycle arrest in TECs.
  • TGF-β1 and FGF-2 were found to negatively regulate JLP expression.

Conclusions:

  • JLP functions as a key endogenous antifibrotic factor in the kidney.
  • JLP exerts protective effects by inhibiting TGF-β1 signaling and associated profibrotic processes.
  • JLP plays a critical role in renal fibrosis through its interaction with TGF-β1.

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