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TRPC5 Channel Inhibition Protects Podocytes in Puromycin-Aminonucleoside Induced Nephrosis Models

Yiming Zhou1,2, Choah Kim2, Juan Lorenzo B Pablo2

  • 1Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.

Frontiers in Medicine
|October 8, 2021
PubMed

Insights

TRPC5 channel inhibition protects podocytes from injury and reduces proteinuria in kidney disease models. This study confirms the therapeutic potential of TRPC5 inhibitors for treating progressive kidney diseases.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pharmacology

Background:

  • Podocyte injury and proteinuria characterize progressive kidney diseases.
  • TRPC5 channel inhibition shows promise in rodent models, but human relevance is unclear.

Purpose of the Study:

  • Investigate TRPC5 inhibition effects in PAN-induced nephrosis rats, human iPSC-derived podocytes, and kidney organoids.
  • Assess the therapeutic potential of TRPC5 inhibition for kidney disease.

Main Methods:

  • Administered TRPC5 inhibitor AC1903 to PAN-treated rats.
  • Recorded and blocked TRPC5 currents in human iPSC-derived podocytes.
  • Induced podocyte injury using PAN in 2D and 3D human cell/organoid cultures.

Main Results:

  • AC1903 protected podocyte cytoskeletal proteins and suppressed proteinuria in rats.
  • TRPC5 inhibition reversed PAN-induced podocyte injury in human cells and organoids.
  • TRPC5 channel activity was confirmed and blocked in human podocytes.

Conclusions:

  • TRPC5 channel inhibition is relevant for puromycin aminonucleoside-induced nephrosis.
  • TRPC5 inhibition demonstrates therapeutic potential for progressive kidney diseases.
Keywords:
Rac1TRPC5 channelcalcium signalingkidney diseasepodocyte

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