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Updated: Oct 1, 2025

Simultaneous Study of the Recruitment of Monocyte Subpopulations Under Flow In Vitro
09:16

Simultaneous Study of the Recruitment of Monocyte Subpopulations Under Flow In Vitro

Published on: November 26, 2018

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Indoxyl sulfate- and P-cresol-induced monocyte adhesion and migration is mediated by integrin-linked kinase-dependent

Sofía Campillo1,2, Lourdes Bohorquez1,2, Elena Gutiérrez-Calabrés1,2

  • 1Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Alcalá de Henares, Spain.

Experimental & Molecular Medicine
|March 5, 2022
PubMed

Insights

Cardiovascular disease in chronic kidney disease (CKD) is linked to uremic toxins. These toxins promote monocyte adhesion and migration via integrin-linked kinase (ILK) and podosome formation, suggesting ILK as a therapeutic target for vascular injury.

Area of Science:

  • Nephrology
  • Cardiology
  • Cell Biology

Background:

  • Cardiovascular disease is a major cause of mortality in chronic kidney disease (CKD) patients.
  • Protein-bound uremic toxins, like p-cresol and indoxyl sulfate (IS), accumulate due to poor removal during hemodialysis.
  • These toxins contribute to vascular endothelial dysfunction and leukocyte extravasation, processes potentially mediated by podosomes.

Purpose of the Study:

  • To investigate the role of integrin-linked kinase (ILK) and podosome formation in monocyte adhesion and extravasation under exposure to p-cresol (pc) and IS.
  • To elucidate the signaling pathways involved in toxin-induced monocyte activation.

Main Methods:

  • Incubation of THP-1 human monocyte cells and leukocytes from wild-type and ILK-knockdown mice with pc and IS.
  • Assessment of ILK kinase activity, cell adhesion, podosome formation, extracellular matrix degradation, and migration.
  • Depletion of ILK, Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP), and AKT using small interfering RNAs (siRNAs).
  • Immunofluorescence microscopy to analyze the colocalization of F-actin, cortactin, and ILK in podosomes.

Main Results:

  • Exposure to pc and IS upregulated ILK kinase activity in THP-1 cells.
  • Both toxins enhanced monocyte adhesion, podosome formation, ECM degradation, and migration, effects suppressed by ILK depletion.
  • ILK depletion abrogated toxin-induced adhesion and podosome formation in mouse leukocytes.
  • ILK colocalized with cortactin in podosome rings, while F-actin colocalized in podosome cores.
  • The ILK/AKT signaling pathway was implicated in toxin-induced monocyte adhesion dependent on podosome formation.

Conclusions:

  • P-cresol and indoxyl sulfate stimulate monocyte podosome formation and enhance their migratory capacity through an ILK/AKT signaling pathway.
  • This process contributes to vascular injury in CKD patients.
  • Integrin-linked kinase (ILK) represents a potential therapeutic target for mitigating vascular damage associated with CKD.

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