Identification of a common molecular pathway in hypertensive renal damage

Skogstrand, T., Leh, S., McClure, J. , Dashti, M., Iversen, B. M., Graham, D. , McBride, M. and Hultström, M. (2015) Identification of a common molecular pathway in hypertensive renal damage. Journal of Hypertension, 33(3), pp. 584-596. (doi: 10.1097/HJH.0000000000000395) (PMID:25380151)

Abstract

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

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Graham, Dr Delyth and McBride, Dr Martin and McClure, Dr John
• Authors: Skogstrand, T., Leh, S., McClure, J., Dashti, M., Iversen, B. M., Graham, D., McBride, M., and Hultström, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of Hypertension
• Publisher: Lippincott Williams & Wilkins
• ISSN: 0263-6352
• ISSN (Online): 1473-5598