title: Increased proliferative cells in the medullary thick ascending limb of the loop of Henle in the Dahl salt-sensitive rat.
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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.forename: Francesco C
authors.initials: FC
authors.lastname: Stingo
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Ahn
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Liu
authors.forename: Marina
authors.initials: M
authors.lastname: Vannucci
authors.forename: Purushottam W
authors.initials: PW
authors.lastname: Laud
authors.forename: Meredith
authors.initials: M
authors.lastname: Skelton
authors.forename: Paul
authors.initials: P
authors.lastname: O'Connor
authors.forename: Terry
authors.initials: T
authors.lastname: Kurth
authors.forename: Robert P
authors.initials: RP
authors.lastname: Ryan
authors.forename: Carol
authors.initials: C
authors.lastname: Moreno
authors.forename: Shirng-Wern
authors.initials: SW
authors.lastname: Tsaih
authors.forename: Giannino
authors.initials: G
authors.lastname: Patone
authors.forename: Oliver
authors.initials: O
authors.lastname: Hummel
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Jacob
authors.forename: Mingyu
authors.initials: M
authors.lastname: Liang
authors.forename: Allen W
authors.initials: AW
authors.lastname: Cowley
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008138:Loop of Henle / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D012965:Sodium Chloride / Q000378:metabolism
chemical_list: D012965:Sodium Chloride