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Novel mechanism of transcriptional regulation of cell matrix protein through CREB

Samy L Habib1, Sumathy Mohan, Sitai Liang

  • 1a South Texas Veterans Health Care System ; San Antonio , TX USA.

Cell Cycle (Georgetown, Tex.)
|June 27, 2015
PubMed

Insights

High glucose increases fibronectin in diabetic kidneys via CREB. Rapamycin treatment reverses this by activating AMPK, offering a potential therapy for diabetic kidney complications.

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Diabetic kidney disease is characterized by renal cell matrix accumulation.
  • The precise molecular mechanisms driving this process remain incompletely understood.

Purpose of the Study:

  • To elucidate the transcriptional regulation of fibronectin in diabetic nephropathy.
  • To investigate the role of cAMP-responsive element binding protein (CREB) and AMPK in this process.

Main Methods:

  • In vitro studies using high glucose (HG) and normal glucose (NG) cell cultures.
  • Treatment with rapamycin and siRNA targeting CREB.
  • Western blotting, RT-PCR, promoter activity assays, nuclear translocation studies, and gel shift analysis.
  • In vivo studies using db/db mice.

Main Results:

  • High glucose increased CREB phosphorylation and fibronectin expression in renal cells.
  • Rapamycin treatment and CREB inhibition reduced fibronectin expression and increased AMPK activity.
  • Activated CREB bound to the fibronectin promoter, an effect reversed by rapamycin.
  • In db/db mice, rapamycin decreased p-CREB and fibronectin, while increasing AMPK activity.

Conclusions:

  • A novel mechanism involving CREB-mediated transcriptional regulation of fibronectin in diabetic kidney matrix accumulation is identified.
  • Targeting the CREB pathway, potentially with agents like rapamycin, may offer a therapeutic strategy for diabetic nephropathy.
Keywords:
AMPKCREBcell matrixfibronectinrenal cellstranscription

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