Increased Proliferative Cells in the Medullary Thick Ascending Limb of the Loop of Henle in the Dahl Salt-Sensitive Rat

摘要

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% 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 one week of a high salt diet resulted in a several fold increase in proliferative medullary thick ascending limb cells in both rat strains and that Dahl salt-sensitive rats exhibited significantly greater proportion of medullary thick ascending limb cells in a proliferative state than in SS.13^BN rats (15.0% ± 1.4% vs. 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 two 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.