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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Enhancement of cGMP-dependent pathway activity ameliorates hyperglycemia-induced decrease in SIRT1-AMPK activity in

Dorota Rogacka1, Patrycja Rachubik2, Irena Audzeyenka1

  • 1Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Gdansk, Poland; Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdansk, Gdansk, Poland.

Biochimica Et Biophysica Acta. Molecular Cell Research
|September 24, 2022
PubMed

Insights

Enhancing the cyclic guanosine monophosphate (cGMP) pathway in kidney podocytes improves sirtuin 1 (SIRT1) and adenosine monophosphate-dependent protein kinase (AMPK) crosstalk. This boosts podocyte function and insulin responsiveness under high glucose conditions.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Hyperglycemia impairs kidney podocyte function by decreasing cyclic guanosine monophosphate (cGMP)-dependent pathways.
  • This dysfunction involves reduced crosstalk between sirtuin 1 (SIRT1) and adenosine monophosphate-dependent protein kinase (AMPK), impacting insulin responsiveness.

Purpose of the Study:

  • To investigate the impact of enhancing cGMP-dependent pathway activity on SIRT1-AMPK crosstalk in podocytes under hyperglycemic conditions.
  • To determine if modulating the cGMP pathway can restore podocyte function during hyperglycemia.

Main Methods:

  • Utilized a cGMP analog to enhance cGMP-dependent pathway activity in podocytes.
  • Assessed changes in SIRT1 protein levels and activity.
  • Measured the phosphorylation status of AMPK.
  • Evaluated podocyte function and albumin permeability.

Main Results:

  • Enhancing cGMP pathway activity increased SIRT1 protein levels and activity.
  • Concomitant increase observed in AMPK phosphorylation.
  • Beneficial effects on podocyte function were noted.
  • SIRT1-AMPK crosstalk was linked to albumin permeability regulation.

Conclusions:

  • The cGMP-dependent pathway plays a crucial role in regulating SIRT1-AMPK crosstalk in podocytes during hyperglycemia.
  • Restoring cGMP pathway activity can ameliorate hyperglycemia-induced podocyte dysfunction.
  • SIRT1-AMPK crosstalk is a key mediator of albumin permeability in diabetic kidney disease.
Keywords:
AMPKAlbumin permeabilityGlucose uptakePodocyteSIRT1cGMP

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