Everolimus Stabilizes Podocyte Microtubules via Enhancing TUBB2B and DCDC2 Expression

PloS One
Stefanie JeruschkeStefanie Weber

Abstract

Glomerular podocytes are highly differentiated cells that are key components of the kidney filtration units. The podocyte cytoskeleton builds the basis for the dynamic podocyte cytoarchitecture and plays a central role for proper podocyte function. Recent studies implicate that immunosuppressive agents including the mTOR-inhibitor everolimus have a protective role directly on the stability of the podocyte actin cytoskeleton. In contrast, a potential stabilization of microtubules by everolimus has not been studied so far. To elucidate mechanisms underlying mTOR-inhibitor mediated cytoskeletal rearrangements, we carried out microarray gene expression studies to identify target genes and corresponding pathways in response to everolimus. We analyzed the effect of everolimus in a puromycin aminonucleoside experimental in vitro model of podocyte injury. Upon treatment with puromycin aminonucleoside, microarray analysis revealed gene clusters involved in cytoskeletal reorganization, cell adhesion, migration and extracellular matrix composition to be affected. Everolimus was capable of protecting podocytes from injury, both on transcriptional and protein level. Rescued genes included tubulin beta 2B class IIb (TUBB2B) and doublecortin ...Continue Reading

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Datasets Mentioned

BETA
GSE66107

Methods Mentioned

BETA
GTPase
nucleotide exchange
transmission electron microscopy
sedation
Assay
Chip
protein assay
electrophoresis
dissection
light microscopy

Software Mentioned

Affymetrix GeneChipOperatingSoftware
NIS Elements AR
cellSens Dimension
Image J
Adobe Photoshop
ImageJ
Fusion

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