Increased proliferative cells in the medullary thick ascending limb of the loop of Henle in the Dahl salt-sensitive rat

C Yang, FC Stingo, KW Ahn, P Liu, M Vannucci… - …, 2013 - Am Heart Assoc
C Yang, FC Stingo, KW Ahn, P Liu, M Vannucci, PW Laud, M Skelton, P O'Connor, T Kurth…
Hypertension, 2013Am Heart Assoc
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. 13BN rats on either 0.4% or 7 days of 8.0% NaCl diet (n= 4) were highly …
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.13BN 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.13BN 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.13BN 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.
Am Heart Assoc
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