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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. and Stingo, F.C. and Ahn, K.W. and Liu, P. and Vannucci, M. and Laud, P.W. and Skelton, M. and O’Connor, P. and Kurth, T. and Ryan, R.P. and Moreno, C. and Tsaih, S.W. and Patone, G. and Hummel, O. and Jacob, H.J. and 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 (U.S.A.)
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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