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Temporal analysis of signaling pathways associated with the development of renovascular hypertension
Author(s) -
Grande Joseph Peter,
Cheng Jingfei,
Yin Ping,
Zhou Wei,
Warner Gina M.,
Gray Catherine E.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1210.3
Subject(s) - medicine , kidney , renovascular hypertension , fibrosis , nephrosclerosis , proliferating cell nuclear antigen , endocrinology , muscle hypertrophy , pathology , immunohistochemistry
The objective of this study was to identify signaling pathways leading to the development of interstitial fibrosis and tubular atrophy in the stenotic kidney and compensatory hypertrophy/hyperplasia of the contralateral kidney in a murine 2 kidney 1 clip model of hypertensive nephrosclerosis. Mice were studied 2, 5, and 11 weeks after undergoing surgery to establish unilateral renal artery stenosis (RAS). RAS animals, but not sham controls, became hypertensive within 1 week. Compensatory enlargement of the contralateral kidney was associated with a transient increase in proliferation (as assessed by PCNA and Mib‐1), p‐ERK, caspase 3, p27, p53, and TGF‐β expression at early time points, with return to baseline levels by 11 weeks. Tubular atrophy in the stenotic kidney was associated with a persistent increase in p‐ERK, Mib‐1, p53, p21, and p27 expression through 11 weeks. Proliferative activity was observed in tubular epithelial cells and in inflammatory cells. The atrophic kidneys had little apoptotic activity (caspase 3, TUNEL staining). The atrophic kidneys showed progressive increases in TGF‐β and α‐SMA expression and extracellular matrix deposition throughout 11 weeks. Interstitial inflammation was associated with increased MCP‐1 expression. Mechanisms underlying this differential response to unilateral RAS await definition.