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dc.contributor.authorCampillo De Blas, Sofía
dc.contributor.authorBohorquez Magro, María Lourdes 
dc.contributor.authorGutiérrez Calabrés, Elena 
dc.contributor.authorGarcía Ayuso, Diego 
dc.contributor.authorMiguel, Verónica
dc.contributor.authorGriera Merino, Mercedes 
dc.contributor.authorCalle, Yolanda
dc.contributor.authorFrutos García, Sergio de 
dc.contributor.authorRodríguez Puyol, Manuel Antonio 
dc.contributor.authorRodríguez Puyol, Diego María 
dc.contributor.authorCalleros Basilio, Laura
dc.identifier.bibliographicCitationCampillo, S., Bohorquez, L., Gutiérrez-Calabrés, E. et al. Indoxyl sulfate- and P-cresol-induced monocyte adhesion and migration is mediated by integrin-linked kinase-dependent podosome formation. Exp Mol Med 54, 226–238 (2022).
dc.description13 p.
dc.description.abstractCardiovascular disease is an important cause of death in patients with chronic kidney disease (CKD). Protein-bound uremic toxins, such as p-cresyl and indoxyl sulfate (IS), are poorly removed during hemodialysis, leading to vascular endothelial dysfunction and leukocyte extravasation. These processes can be related to dynamic adhesion structures called podosomes. Several studies have indicated the role of integrin-linked kinase (ILK) in the accumulation of integrin-associated proteins in podosomes. Here, we investigated the involvement of ILK and podosome formation in the adhesion and extravasation of monocytes under p-cresol (pc) and IS exposure. Incubation of THP-1 human monocyte cells with these toxins upregulated ILK kinase activity. Together, both toxins increased cell adhesion, podosome formation, extracellular matrix degradation, and migration of THP-1 cells, whereas ILK depletion with specific small interfering RNAs suppressed these processes. Interestingly, F-actin colocalized with cortactin in podosome cores, while ILK was colocalized in podosome rings under toxin stimulation. Podosome Wiskott-Aldrich syndrome protein (WASP)- interacting protein (WIP) and AKT protein depletion demonstrated that monocyte adhesion depends on podosome formation and that the ILK/AKT signaling pathway is involved in these processes. Ex vivo experiments showed that both toxins induced adhesion and podosome formation in leukocytes from wild-type mice, whereas these effects were not observed in leukocytes of conditional ILK-knockdown animals. In summary, under pc and IS stimulation, monocytes increase podosome formation and transmigratory capacity through an ILK/AKT signaling pathway-dependent mechanism, which could lead to vascular injury. Therefore, ILK could be a potential therapeutic target for the treatment of vascular damage associated with CKD.en
dc.description.sponsorshipMinisterio de Economía y Competitividades
dc.rights© The Author(s) 2022en
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)en
dc.titleIndoxyl sulfate- and P-cresol-induced monocyte adhesion and migration is mediated by integrin-linked kinase-dependent podosome formationen
dc.contributor.affiliationUniversidad de Alcalá. Escuela Politécnica. Direcció
dc.contributor.affiliationUniversidad de Alcalá. Departamento de Medicina y Especialidades Médicases
dc.contributor.affiliationUniversidad de Alcalá. Departamento de Biología de Sistemases
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//RD16%2F0009%2F0018/ES/Red de Investigacion Renal REDINREN/en
dc.identifier.publicationtitleExperimental and Molecular Medicineen

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