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Klotho inhibits PKCα/p66SHC-mediated podocyte injury in diabetic nephropathy

Wei Jiang1, Tangli Xiao1, Wenhao Han1

  • 1Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

Molecular and Cellular Endocrinology
|June 18, 2019
PubMed

Insights

Klotho protein may protect against diabetic nephropathy by inhibiting the PKCα/p66SHC pathway, which contributes to podocyte injury and kidney damage in diabetes.

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Diabetic nephropathy (DN) is a leading cause of kidney disease, characterized by podocyte injury.
  • Protein kinase C alpha (PKCα) and p66SHC are implicated in podocyte injury, but their role in DN is unclear.
  • Klotho, an anti-aging protein, protects the kidney, yet its mechanism in DN remains elusive.

Purpose of the Study:

  • To investigate the role of the Klotho/PKCα/p66SHC pathway in diabetic nephropathy.
  • To elucidate how Klotho ameliorates podocyte injury in the context of DN.

Main Methods:

  • Utilized STZ-induced diabetic mouse models with and without Klotho deficiency.
  • Employed in vitro experiments with high glucose to study podocyte apoptosis.
  • Assessed proteinuria, podocyte injury markers, PKCα, p66SHC, and reactive oxygen species (ROS).

Main Results:

  • Klotho levels were reduced in diabetic mice, and its deficiency exacerbated DN.
  • PKCα and p66SHC activation correlated with podocyte injury and proteinuria in DN.
  • Klotho overexpression partially reversed PKCα/p66SHC-mediated podocyte injury and ROS production.

Conclusions:

  • Klotho may protect against diabetic nephropathy by inhibiting the PKCα/p66SHC pathway.
  • This pathway contributes to high glucose-induced podocyte apoptosis and kidney damage.
  • Klotho represents a potential therapeutic target for managing diabetic nephropathy.
Keywords:
Diabetic nephropathyKlothoPKCαPodocyteReactive oxygen species

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