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p21(WAF1/CIP1) Expression is Differentially Regulated by Metformin and Rapamycin

Zoltan Molnar1, Ann B Millward1, Wai Tse1

  • 1Renal Unit and Diabetes Clinical Research Unit, Derriford Hospital, Plymouth, PL6 8DH, UK.

International Journal of Chronic Diseases
|October 15, 2015
PubMed

Insights

Metformin inhibits high glucose-induced p21 expression in epithelial cells, independent of mTOR signaling. This suggests AMPK activation may regulate p21, impacting diabetic nephropathy and aging.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Endocrinology

Background:

  • The mammalian target of rapamycin (mTOR) pathway is implicated in diabetic nephropathy (DN) and aging.
  • Elevated p21(WAF1/CIP1) expression is a hallmark of DN.
  • The role of mTOR signaling in p21 regulation remains unclear.

Purpose of the Study:

  • To investigate the effects of metformin and rapamycin on mTOR-related phenotypes.
  • To elucidate the role of metformin and rapamycin in regulating p21 expression in epithelial cells.

Main Methods:

  • Utilized epithelial cell lines to study mTOR signaling.
  • Administered metformin and rapamycin under high glucose conditions.
  • Assessed cell size, proliferation, protein synthesis, AMPK activation, and p21 expression.

Main Results:

  • Metformin inhibited high glucose-induced p21 expression.
  • High glucose counteracted metformin's effects on cell size, proliferation, and protein synthesis.
  • Rapamycin's inhibition of mTOR did not affect p21 expression, indicating metformin acts upstream of mTOR.

Conclusions:

  • Metformin regulates p21 expression independently of direct mTOR pathway inhibition.
  • AMPK activation by metformin may be responsible for p21 regulation.
  • Findings suggest potential therapeutic implications for diabetic nephropathy and age-related diseases.

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