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
Date
11/28/2012Pubmed ID
23184381Pubmed Central ID
PMC3760736DOI
10.1161/HYPERTENSIONAHA.112.199380Scopus ID
2-s2.0-84871619201 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
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 JrAuthors
Kwang Woo Ahn PhD Professor in the Institute for Health and Equity department at Medical College of WisconsinAllen 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
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCell Cycle
Cell Proliferation
Gene Expression Profiling
Gene Expression Regulation
Hypertension
Loop of Henle
Male
Rats
Rats, Inbred Dahl
Sodium Chloride
