Increased proliferative cells in the medullary thick ascending limb of the loop of henle in the dahl salt-sensitive rat

Chun Yang, Francesco C. Stingo, Kwang Woo Ahn, Pengyuan Liu, Marina Vannucci, Purushottam W. Laud, Meredith Skelton, Paul O'Connor, Terry Kurth, Robert P. Ryan, Carol Moreno, Shirng Wern Tsaih, Giannino Patone, Oliver Hummel, Howard J. Jacob, Mingyu Liang, Allen W. Cowley

Research output: Contribution to journalArticle

15 Scopus citations

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 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 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 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.

Original languageEnglish (US)
Pages (from-to)208-215
Number of pages8
JournalHypertension
Volume61
Issue number1
DOIs
StatePublished - Jan 1 2013

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Keywords

  • cell cycle
  • gene expression
  • kidney

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Yang, C., Stingo, F. C., Ahn, K. W., Liu, P., Vannucci, M., Laud, P. W., Skelton, M., O'Connor, P., Kurth, T., Ryan, R. P., Moreno, C., Tsaih, S. W., Patone, G., Hummel, O., Jacob, H. J., Liang, M., & Cowley, A. W. (2013). Increased proliferative cells in the medullary thick ascending limb of the loop of henle in the dahl salt-sensitive rat. Hypertension, 61(1), 208-215. https://doi.org/10.1161/HYPERTENSIONAHA.112.199380