A common core of extracellular matrix and cell-matrix binding genes is activated during the development of hypertensive kidney damage across different rat models.
Conserved ECM gene activation across rat hypertensive kidney models; hypothesis-generating for human mechanisms and therapies.
Introduction The aim of this work was to identify common genetic pathways in kidneys of three hypertensive rat models during development of kidney damage. Methods Kidney microarray expression profiles were determined from 60‐week‐old Spontaneously Hypertensive Rats (SHR) versus Wistar Kyoto (WKY); 21‐week‐old salt‐loaded Stroke‐Prone SHR (SHRSP), and 30‐week‐old Wistar rats with two kidney, one clip (2K1C) hypertension for 24 weeks versus sham‐operated controls. Results Differentially expressed genes (FDR < 0.05: 2033 in 2K1C, 3721 in SHR, and 519 in SHRSP) identified 93 common between models. Top genes by rank‐sum were: SPP1, TIMP1, LCN2, COL3A1, WTAP, FN1, KIFC1, SLPI, MGP, TNFRSF12A. Analysis of gene ontology showed enrichment in extracellular matrix (p<2e‐8), cell‐substrate adhesion (p<0.001), defence response (p<1e‐4), and protein binding (p<0.005). Ingenuity Pathway Analysis identified cardiovascular inflammation (p<1e‐8) and renal injury (p<1e‐5) as two major activated pathways. Conclusion Comparing three models of hypertensive kidney damage identify a common core of extracellular matrix and cell‐matrix binding genes activated during the development of kidney damage in hypertension. Funding from the Health Authority of Western Norway, Haukeland University Hospital Strategic Research, Lars Hiertas Minne, Magn. Bergvall, British Heart Founation.
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Skogstrand et al. (2012) studied this question.
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