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Induction of Mindin is Associated with Pathological Changes in the Kidney of Cd151 ‐/‐ Mice
Author(s) -
Naudin Crystal,
Weidenhofer Judith,
Roselli Severine,
Keely Simon
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb437
Subject(s) - biology , podocyte , actin cytoskeleton , immune system , kidney , pathology , immunology , cytoskeleton , cell , medicine , endocrinology , genetics , proteinuria
The presence of CD151, a transmembrane protein involved in cell adhesion complexes with α3β1 integrins, is essential for glomerular function. We have identified significant increases in mindin in the glomeruli of CD151 knock‐out mice ( Cd151 ‐/‐ )compared to wild‐types ( Cd151 +/+ ). Due to mindins known role in actin cytoskeleton and cell adhesion signalling, we hypothesised that aberrant expression of mindin in the glomerulus leads to the abnormal extracellular matrix deposition, and disruption to podocyte actin cytoskeleton structure, which occurs in this disease model. Immunofluorescent labelling of mindin in 3‐week‐old Cd151 +/+ and Cd151 ‐/‐ kidneys demonstrated specific accumulation in Cd151 ‐/‐ glomeruli, (absent in Cd151 +/+ ). No expression of mindin was observed in 5 day old mice (when Cd151 ‐/‐ glomeruli first exhibit pathology) indicating it is unlikely to be involved in initial pathology. As mindin is also an immune cell activator, we examined whether the induction of mindin leads to immune‐mediated glomerular injury as part of disease progression in the Cd151 ‐/‐ kidney. We also investigated mindin as a potential biomarker of glomerular disease in the broader sense and characterised immune cell infiltrates in Cd151 ‐/‐ kidneys. Infiltration of lymphocytes, neutrophils, macrophages and eosinophils was observed as early as 3 weeks of age in Cd151 ‐/‐ but not Cd151 +/+ kidneys by differential histological staining. This infiltration was progressive and more pronounced in 12 week old Cd151 ‐/‐ mice, associated with extensive inflammatory lesions. Together, these data suggest that in the absence of CD151, mindin is induced early in disease, associated with disruption to podocyte actin cytoskeleton homeostasis, and immune‐mediated glomerular damage.