Norepinephrine Enhances Fibrosis Mediated by TGF-β in Cardiac Fibroblasts

Abstract

Cardiac fibrosis results from proliferation of interstitial fibroblasts and concomitant increased biosynthesis of extracellular matrix (ECM) components and is often complicated by cardiac hypertrophy. This study was conducted to investigate whether norepinephrine (NE) potentiates transforming growth factor-β (TGF-β)–induced cardiac fibrosis. The expression of the cardiac ECM proteins, plasminogen activator inhibitor-1 (PAI-1), fibronectin, and collagen type I, was examined by Western blotting using extracts from neonatal rat primary cardiac fibroblasts. In cardiac fibroblasts, treatment with a combination of NE and TGF-β1 increased cell proliferation and ECM expression. Luciferase assays were conducted to clarify the effect of NE on TGF-β signaling. TGF-β1 (1 ng/mL) increased the specific signaling activity 2-fold, whereas the combination of NE (10 μmol/L) and TGF-β1 (1 ng/mL) resulted in an approximate 10-fold increase in specific signaling activity. We confirmed that treatment with NE markedly enhances ...