Aldosterone/NaCl-induced renal and cardiac fibrosis is modulated by TGF-beta responsiveness of T cells

作者：Schreier Barbara^*; Rabe Sindy; Schneider Bettina; Ruhs Stefanie; Grossmann Claudia; Hauptmann Steffen; Blessing Manfred; Neumann Joachim; Gekle Michael

来源：Hypertension Research, 2011, 34(5): 623-629.

DOI：10.1038/hr.2011.16

• aldosterone
• heart
• kidney
• T cells
• TGF-beta type II receptor

We examined the contribution of transforming growth factor (TGF)-beta-T-cell signaling to aldosterone (aldo)/salt-induced fibrosis in the kidneys and the hearts of FVB/N wild-type (WT) or transgenic (Tg) mice expressing a dominant-negative TGF-beta type II receptor in T cells (hCD2-Delta kTbRII). Animals received aldo through osmotic minipumps and had access to either 1% NaCl (aldo/NaCl group) or tap water (vehicle group) for 4 weeks. Systolic blood pressure was measured during this period via a tail cuff. The animals were then killed, and urine, blood, kidneys and hearts were collected. Systolic blood pressure did not differ between the groups. Aldo/NaCl enhanced renal, cardiac and left ventricular weight in WT animals slightly, but only renal weight was increased in Tg animals. Urinary protein excretion was enhanced in Tg animals (fourfold) and increased further in WT (twofold) and Tg (1.8-fold) mice on aldo/NaCl treatment. Aldo/NaCl increased interstitial fibrosis in the kidneys (1.5-fold) and the hearts of WT (2.5-fold) animals. Under control conditions, Tg mouse cardiac (3.2-fold) and renal (1.7-fold) tissues were slightly more fibrotic compared with WT, and this condition was not further aggravated by aldo/NaCl. Aldo/NaCl-induced mRNA expression of renal fibronectin (10.7-fold in WT) but not of renal collagen mRNA expression (WT: Col1a1 7.7-fold; Col3a1, 3.1-fold; and Col4a1 3.3-fold) was abrogated in Tg animals. In hearts, aldo/NaCl-induced plasminogen activator inhibitor-1 mRNA (twofold) expression depended on TGF-beta-T-cell signaling. Our results indicate that (i) aldo/NaCl can induce renal and cardiac damage in the absence of blood pressure changes, (ii) the elimination TGF-beta-T-cell cross-talk leads to renal and cardiac fibrosis but does not exacerbate aldo/NaCl-induced damage and (iii) the pathological aldo/NaCl effect is modified, in part, by TGF-beta-T-cell cross-talk. Hypertension Research (2011) 34, 623-629; doi:10.1038/hr.2011.16; published online 24 February 2011

• 出版日期2011-5