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Shear stress induces cell apoptosis via a c-Src-phospholipase D-mTOR signaling pathway in cultured podocytes

Chunfa Huang1, Leslie A Bruggeman, Lindsey M Hydo

  • 1Louis Stokes Cleveland Veteran Affairs Medical Center, Case Western Reserve University, USA. chunfa.huang@case.edu

Experimental Cell Research
|April 5, 2012
PubMed

Insights

Shear stress on kidney podocytes triggers apoptosis by activating c-Src, phospholipase D (PLD), and mammalian target of rapamycin (mTOR) signaling, leading to kidney disease progression.

Area of Science:

  • Nephrology
  • Cell Biology
  • Mechanobiology

Background:

  • The glomerular capillary wall endures hemodynamic forces, and abnormal forces like hyperfiltration cause kidney injury.
  • The mechanisms by which podocytes convert mechanical stimuli into chemical signals are not fully understood.

Purpose of the Study:

  • To investigate the molecular mechanisms by which shear stress induces apoptosis in podocytes.
  • To elucidate the role of c-Src, phospholipase D (PLD), and mammalian target of rapamycin (mTOR) signaling in shear stress-induced podocyte injury.

Main Methods:

  • Cultured podocytes were subjected to shear stress.
  • Assays for DNA fragmentation, apoptotic nuclear changes, and cytochrome c release were performed.
  • Western blotting, co-immunoprecipitation, and in vitro PLD activity assays were used to study signaling pathways.

Main Results:

  • Shear stress induced apoptosis in cultured podocytes.
  • Shear stress activated c-Src phosphorylation, PLD activation, and mTOR signaling.
  • c-Src interacted with and activated PLD(1), leading to phosphatidic acid production, which stimulated mTOR signaling and caused podocyte hypertrophy and apoptosis.

Conclusions:

  • Shear stress is a direct inducer of apoptosis in podocytes.
  • The c-Src-PLD-mTOR signaling pathway mediates shear stress-induced podocyte injury.
  • Understanding these mechanisms may offer therapeutic targets for progressive renal disease.

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