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Ste20-like kinase, SLK, a novel mediator of podocyte integrity

Andrey V Cybulsky1, Joan Papillon1, Julie Guillemette1

  • 1Department of Medicine, McGill University Health Centre Research Institute, McGill University , Montreal, Quebec , Canada.

American Journal of Physiology. Renal Physiology
|December 1, 2017
PubMed

Insights

The serine/threonine kinase SLK is crucial for maintaining podocyte integrity. Deleting SLK in podocytes leads to kidney injury, albuminuria, and podocyte loss in aging mice.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Serine/threonine kinase SLK (SLK) is vital for embryonic development and implicated in wound healing, tumor growth, and metastasis.
  • SLK expression and activation are elevated during kidney development and ischemic acute kidney injury recovery.
  • Dysregulated SLK in podocytes causes injury and proteinuria, highlighting its importance in renal function.

Purpose of the Study:

  • To investigate the functional role of SLK in podocytes using a podocyte-specific SLK-knockout mouse model.
  • To determine the impact of SLK deletion on podocyte structure, function, and overall renal health.

Main Methods:

  • Generation of podocyte-specific SLK-knockout mice.
  • Assessment of glomerular SLK expression and activity.
  • Evaluation of urinary albumin levels, podocyte ultrastructure, podocyte number, and expression of key podocyte markers (nephrin, synaptopodin, podocalyxin).

Main Results:

  • Podocyte-specific SLK deletion resulted in reduced glomerular SLK expression and activity.
  • Knockout mice developed progressive albuminuria, starting at 4-5 months in males and 8-9 months in females.
  • Ultrastructural analysis revealed podocyte foot process effacement, microvillous transformation, reduced podocyte number, and decreased expression of podocyte-specific proteins.

Conclusions:

  • SLK is essential for maintaining podocyte integrity and normal renal structure and function.
  • Loss of SLK in podocytes leads to age-dependent albuminuria, podocyte depletion, and morphological damage.
  • Targeting SLK may offer therapeutic potential for kidney diseases involving podocyte injury.
Keywords:
albuminuriacytoskeletonglomeruluskidneyknockout mouse

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