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Increased proliferative cells in the medullary thick ascending limb of the loop of henle in the dahl salt-sensitive rat

Item Type:Article
Title:Increased proliferative cells in the medullary thick ascending limb of the loop of henle in the dahl salt-sensitive rat
Creators Name:Yang, C., Stingo, F.C., Ahn, K.W., Liu, P., Vannucci, M., Laud, P.W., Skelton, M., O’Connor, P., Kurth, T., Ryan, R.P., Moreno, C., Tsaih, S.W., Patone, G., Hummel, O., Jacob, H.J., Liang, M. and Cowley, A.W.
Abstract:Studies of transcriptome profiles have provided new insights into mechanisms underlying the development of hypertension. Cell type heterogeneity in tissue samples, however, has been a significant hindrance in these studies. We performed a transcriptome analysis in medullary thick ascending limbs of the loop of Henle isolated from Dahl salt-sensitive rats. Genes differentially expressed between Dahl salt-sensitive rats and salt-insensitive consomic SS.13(BN) rats on either 0.4% or 7 days of 8.0% NaCl diet (n=4) were highly enriched for genes located on chromosome 13, the chromosome substituted in the SS.13(BN) rat. A pathway involving cell proliferation and cell cycle regulation was identified as one of the most highly ranked pathways based on differentially expressed genes and by a Bayesian model analysis. Immunofluorescent analysis indicated that just 1 week of a high-salt diet resulted in a severalfold increase in proliferative medullary thick ascending limb cells in both rat strains, and that Dahl salt-sensitive rats exhibited a significantly greater proportion of medullary thick ascending limb cells in a proliferative state than in SS.13(BN) rats (15.0±1.4% versus 10.1±0.6%; n=7-9; P<0.05). The total number of cells per medullary thick ascending limb section analyzed was not different between the 2 strains. The study revealed alterations in regulatory pathways in Dahl salt-sensitive rats in tissues highly enriched for a single cell type, leading to the unexpected finding of a greater increase in the number of proliferative medullary thick ascending limb cells in Dahl salt-sensitive rats on a high-salt diet.
Keywords:Kidney, Gene Expression, Cell Cycle, Animals, Rats
Source:Hypertension
ISSN:0194-911X
Publisher:American Heart Association
Volume:61
Number:1
Page Range:208-215
Date:January 2013
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.112.199380
PubMed:View item in PubMed

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