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Matrix metalloproteinase‐9 mediated shedding of syndecan‐4 in glomerular endothelial cells
Author(s) -
Reine Trine M.,
Lanzalaco Francesca,
Kristiansen Oddrun,
Enget Anne Randi,
Satchell Simon,
Jenssen Trond G.,
Kolset Svein O.
Publication year - 2019
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12534
Subject(s) - syndecan 1 , glycocalyx , diabetic nephropathy , gene knockdown , matrix metalloproteinase , podocyte , microbiology and biotechnology , diabetes mellitus , endocrinology , medicine , biology , cancer research , chemistry , cell , gene , kidney , proteinuria , biochemistry
Background Diabetic nephropathy is the most common cause of end‐stage renal failure in the western world and Asia. The mechanisms are not fully elucidated, but disruption of glomerular endothelial glycocalyx and shedding of its components including syndecans has been implicated. Aims We hypothesize that reduced glomerular filtration in diabetes is caused by disruption of endothelial glycocalyx in glomeruli, including increased shedding of syndecan‐4. The aim of this study was to determine the effects of experimental diabetic conditions by means of hyperglycemia and IL ‐1β exposure on syndecan‐4 shedding in GEnC, and to investigate regulation of shedding by sheddases. Results We found that in GE nC the expression of syndecan‐4 is higher than that of the other syndecans. In polarized GE nC, apical shedding of syndecan‐4 and syndecan‐4 gene expression was increased by 60% after IL ‐1β‐stimulation, but not affected by hyperglycemic conditions. This was accompanied by a 50% increase in MMP 9 gene expression in IL ‐1β‐stimulated cells but not hyperglycemia. MMP 9 knockdown reduced syndecan‐4 shedding by 50%. Conclusion IL ‐1β but not hyperglycemia increases the shedding of syndecan‐4 from GE nC in an MMP 9‐dependent manner. This provides a potential mechanism of GE nC damage in diabetes and other inflammatory conditions.