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Dysfunction of the Klotho-miR-30s/TRPC6 axis confers podocyte injury

Xia Qiu1, Jie Huo1, Shiguo Xia2

  • 1Department of Nephrology, The People's Hospital of Nanchuan, No. 16 South Street, Nanchuan District, Chongqing, 408400, China.

Biochemical and Biophysical Research Communications
|April 16, 2021
PubMed

Insights

Klotho deficiency worsens kidney disease by harming podocytes. Restoring Klotho boosts miR-30a, reducing podocyte injury and proteinuria in a novel therapeutic pathway.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Genetics

Background:

  • Klotho deficiency is prevalent in kidney diseases and implicated in podocyte injury.
  • The precise mechanisms linking Klotho deficiency to podocyte damage are not fully understood.
  • MicroRNAs (miRNAs), including the miR-30 family, are crucial for maintaining podocyte health.

Purpose of the Study:

  • To elucidate the underlying mechanisms of podocyte injury in Klotho deficiency.
  • To investigate the role of miR-30s in the context of Klotho deficiency and podocyte damage.
  • To explore potential therapeutic strategies involving Klotho and miR-30s.

Main Methods:

  • Utilized PAN-treated podocytes and a rat model of kidney injury.
  • Assessed Klotho, miR-30s, and target gene expression (Ppp3ca, Ppp3cb, Ppp3r1, Nfact3, TRPC6).
  • Investigated the effects of Klotho overexpression and exogenous Klotho administration.

Main Results:

  • Klotho and miR-30s were downregulated in PAN-induced podocyte injury.
  • Klotho upregulation ameliorated podocyte apoptosis by modulating miR-30a and its targets.
  • Klotho regulates TRPC6 via miR-30a, impacting calcium/calcineurin signaling.
  • Dexamethasone maintained Klotho and miR-30a levels in vitro.
  • Exogenous Klotho administration in rats reduced podocyte injury and proteinuria.

Conclusions:

  • Klotho, through miR-30s, directly regulates target genes contributing to PAN-induced podocyte apoptosis.
  • This pathway represents a novel mechanism underlying podocyte injury in kidney disease.
  • Targeting the Klotho-miR-30s axis may offer a new therapeutic approach for kidney diseases.
Keywords:
KlothoPodocyteTRPC6miR-30a

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