Renal Regional Proteomes in Young Dahl Salt-Sensitive Rats

Abstract

Abstract-We performed an extensive proteomic analysis of the Dahl model of salt-sensitive hypertension. The consomic SS-13 BN rat, genetically similar to the Dahl salt-sensitive rat, while exhibiting a significant amelioration of salt-induced hypertension, was used as a control. Proteomic analysis, using differential in-gel electrophoresis and mass spectrometry techniques, was performed in the renal cortex and the renal medulla of 6-week-old SS and SS-13 BN rats before significant differences in blood pressure were developed between the 2 strains of rat. Several dozen proteins were identified as differentially expressed between SS and SS-13 BN rats fed the 0.4% NaCl diet or switched to the 4% NaCl diet for 3 days (nϭ4). The identified proteins were involved in cellular functions or structures including signal transduction, energy metabolism, and the cytoskeleton. The proteomic analysis and subsequent Western blotting indicated that heterogeneous nuclear ribonucleoprotein K in the renal medulla was upregulated by the 4% NaCl diet in SS-13 BN rats but downregulated in SS rats. The level of angiotensinogen mRNA in the renal medulla was regulated in an opposite manner. Silencing of heterogeneous nuclear ribonucleoprotein K resulted in an upregulation of angiotensinogen in cultured human kidney cells. In summary, we identified significant differences in kidney regional proteomic profiles between SS and SS-13 BN rats and demonstrated a potential role of heterogeneous nuclear ribonucleoprotein K in the regulation of angiotensinogen expression in the renal medulla. (Hypertension. 2008;51:899-904.)

Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension

“…Yet another possibility is that excess glucocorticoids might upregulate local expression of angiotensinogen in the renal medulla, reminiscent of the observations in mice overexpressing 11␤-HSD1 (28,31). We recently found that angiotensinogen expression in the renal medulla was upregulated by a high-salt diet in SS rats but downregulated in SS-13 BN rats (44).…”

miR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by HIF-α activation

“…HK-2, a human kidney epithelial cell line, was obtained from and cultured as suggested by American Type Culture Collection (48,49). Cells at ϳ40% confluence were treated with recombinant human transforming growth factor (TGF)-␤1 (3 ng/ml, R&D Systems) or the vehicle control in DMEM for the indicated time period.…”

“…The relative abundance of several proteins was analyzed using Western blotting or immunohistochemistry (IHC) as we described previously (3,16,21,27,48,53). Antibodies were from Sigma-Aldrich, Abcam, Novus Biologicals, Bioworld, or Jackson ImmunoResearch.…”

Dynamic convergence and divergence of renal genomic and biological pathways in protection from Dahl salt-sensitive hypertension

“…This is illustrated by our previous work on molecular networks underlying Dahl salt-sensitive hypertension, which has led to several novel discoveries regarding the overall network (9) and specific components of the network (11,20,22,23).…”