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Increased proliferative cells in the medullary thick ascending limb of the loop of Henle in the Dahl salt-sensitive rat. Hypertension 2013 Jan;61(1):208-15 PMID: 23184381 PMCID: PMC3760736

Pubmed ID

23184381

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.

Author List

Yang C, Stingo FC, Ahn KW, Liu P, Vannucci M, Laud PW, Skelton M, O'Connor P, Kurth T, Ryan RP, Moreno C, Tsaih SW, Patone G, Hummel O, Jacob HJ, Liang M, Cowley AW Jr

Authors

Kwang Woo Ahn PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Purushottam W. Laud PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Mingyu Liang PhD Center Director, Professor in the Physiology department at Medical College of Wisconsin
Pengyuan Liu PhD Adjunct Associate Professor in the Physiology department at Medical College of Wisconsin




Scopus

2-s2.0-84871619201   15 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Cell Cycle
Cell Proliferation
Gene Expression Profiling
Gene Expression Regulation
Hypertension
Loop of Henle
Male
Rats
Rats, Inbred Dahl
Sodium Chloride
jenkins-FCD Prod-300 626508253d14e4184314fb9f66322a03a5906796