Identification of a common molecular pathway in hypertensive renal damage: comparison of rat and human gene expression profiles

Skogstrand, T. and Leh, S. and McClure, J. and Dashti, M. and Iversen, B. M. and Graham, D. and McBride, M. W. and Hultstom, M. (2016) Identification of a common molecular pathway in hypertensive renal damage: comparison of rat and human gene expression profiles. [Data Collection]

Collection description

Background: There is a common structural progression in hypertensive renal damage with early arterial damage and fibrosis in the juxtamedullary cortex.

Method: The present investigation identifies a common pathway using three-gene expression profiles from hypertensive rat models: 60-week-old spontaneously hypertensive rat (SHR), salt-loaded stroke-prone SHR (SHRSP), and the non-clipped kidney after 24 weeks of two-kidney, one-clip hypertension (2K1C). Kidney damage was scored using a specialized system. Gene-expression profiles were determined using microarrays and validated using a panel of 47 genes by quantitative real-time PCR.

Results: All groups showed kidney damage (SHRs: 0.32 ± 0.09 vs. Wistar–Kyoto rats: 0.06 ± 0.03; 2K1C: 0.27 ± 0.13 vs. pooled controls: 0.01 ± 0.01; SHRSP: 1.13 ± 0.14 vs. WKY: 0.04 ± 0.03; all P < 0.05). A total of 1614 genes were changed in the SHR experiment, 1323 in the SHRSP, and 576 in the 2K1C. Eighty-eight genes were similarly regulated in all three models. Gene ontology enrichment analysis identified 59 ontologies that were enriched in all three datasets. These included over-representation to extracellular matrix, response to oxidative stress, and immune system processes. Out of the 88 in-common genes, 40 could be connected in a common pathway that was compared to two gene-expression profiles from human kidneys with histologically verified fibrosis to identify a highly significant number of in-common genes that were also represented in the common genetic pathway.

Conclusion: There is a common pathway during the development of hypertensive kidney damage in rats irrespective of model. Interestingly, large parts of this common pathway are conserved in human kidney damage, which may indicate a broader importance in the development of chronic kidney disease.

College / School: College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Date Deposited: 03 May 2016 11:52
Enlighten Publications URL: http://eprints.gla.ac.uk/104158/
URI: http://researchdata.gla.ac.uk/id/eprint/280

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Skogstrand, T. and Leh, S. and McClure, J. and Dashti, M. and Iversen, B. M. and Graham, D. and McBride, M. W. and Hultstom, M. (2016); Identification of a common molecular pathway in hypertensive renal damage: comparison of rat and human gene expression profiles

University of Glasgow

http://researchdata.gla.ac.uk/280

Retrieved: 2017-09-22