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Positive feedback loop between MAPK and aquaporin 7 regulates autophagy and apoptosis induced by palmitate in RIN-m5f

Maoqi Wang1, Jiang Tan1,2, Xueting He1

  • 1Department of Anatomy, Institute of Neuroscience, College of Basic Medicine, Chongqing Medical University, China.

FEBS Open Bio
|March 24, 2025
PubMed

Insights

Aquaporin 7 (AQP7) regulates autophagy and apoptosis in pancreatic beta cells. Reduced AQP7 promotes cell death and inhibits autophagy via MAPK signaling, while its overexpression protects against apoptosis.

Area of Science:

  • Cell Biology
  • Endocrinology
  • Molecular Biology

Background:

  • Type 2 diabetes mellitus (T2DM) involves insulin resistance and pancreatic beta-cell dysfunction.
  • Beta-cell apoptosis is a key factor in T2DM progression.
  • Aquaporin 7 (AQP7) is expressed in pancreatic beta-cells, but its role in autophagy and apoptosis is unclear.

Purpose of the Study:

  • To investigate the role of AQP7 in autophagy and apoptosis of pancreatic beta-cells.
  • To elucidate the underlying molecular mechanisms involving MAPK signaling pathways.

Main Methods:

  • Used palmitate-treated rat pancreatic beta-cells (RIN-m5f) as an in vitro model.
  • Examined AQP7 expression, LC3 lipidation, and p62 expression.
  • Assessed the impact of AQP7 knockdown and overexpression on apoptosis and autophagy.
  • Analyzed the activation of p38 and JNK signaling pathways.

Main Results:

  • Palmitate treatment decreased AQP7 expression, inhibited autophagy, and increased apoptosis.
  • AQP7 knockdown activated p38 and JNK pathways, reduced autophagy, and enhanced apoptosis.
  • AQP7 overexpression suppressed palmitate-induced apoptosis and autophagy inhibition by inhibiting p38 and JNK MAPK pathways.

Conclusions:

  • AQP7 plays a protective role against palmitate-induced apoptosis and autophagy inhibition in pancreatic beta-cells.
  • A feedback loop exists between MAPK signaling and AQP7, regulating autophagy and apoptosis under high-fat conditions.
Keywords:
MAPKapoptosisaquaporin 7autophagypalmitate

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