- Title
- Characterization of the early molecular changes in the glomeruli of Cd151-/- mice highlights induction of mindin and MMP-10
- Creator
- Naudin, Crystal; Smith, Brian; Bond, Danielle R.; Dun, Matthew D.; Scott, Rodney J.; Ashman, Leonie K.; Weidenhofer, Judith; Roselli, Séverine
- Relation
- Scientific Reports Vol. 7, Issue 1, no. 15987, p. 15987-15987
- Publisher Link
- http://dx.doi.org/10.1038/s41598-017-15993-3
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2017
- Description
- In humans and FVB/N mice, loss of functional tetraspanin CD151 is associated with glomerular disease characterised by early onset proteinuria and ultrastructural thickening and splitting of the glomerular basement membrane (GBM). To gain insight into the molecular mechanisms associated with disease development, we characterised the glomerular gene expression profile at an early stage of disease progression in FVB/N Cd151-/- mice compared to Cd151+/+ controls. This study identified 72 up-regulated and 183 down-regulated genes in FVB/N Cd151-/- compared to Cd151+/+ glomeruli (p<0.05). Further analysis highlighted induction of the matrix metalloprotease MMP-10 and the extracellular matrix protein mindin (encoded by Spon2) in the diseased FVB/N Cd151-/- GBM that did not occur in the C57BL/6 diseased-resistant strain. Interestingly, mindin was also detected in urinary samples of FVB/N Cd151-/- mice, underlining its potential value as a biomarker for glomerular diseases associated with GBM alterations. Gene set enrichment and pathway analysis of the microarray dataset showed enrichment in axon guidance and actin cytoskeleton signalling pathways as well as activation of inflammatory pathways. Given the known function of mindin, its early expression in the diseased GBM could represent a trigger of both further podocyte cytoskeletal changes and inflammation, thereby playing a key role in the mechanisms of disease progression.
- Subject
- tetraspanin CD151; glomerular disease; proteinuria; glomerular basement membrane; disease development
- Identifier
- http://hdl.handle.net/1959.13/1392940
- Identifier
- uon:33471
- Identifier
- ISSN:2045-2322
- Rights
- © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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