Transforming growth factor-β1 upregulation is independent of angiotensin in paraquat-induced lung fibrosis

Abstract

Transforming growth factor-β1 (TGF-β1) contributes to the fibrosis of injured organs. Angiotensin II (Ang II) is an inducer of TGF-β1 in cells of the heart and kidneys, and the regulation of TGF-β1 by Ang II has not yet been confirmed in lung tissue. We evaluated the role of TGF-β1 and its relationship with Ang II in paraquat-induced lung fibrosis. Adult male Sprague–Dawley rats were treated intraperitoneally with paraquat (20 mg/kg) or saline in the control group. On days 1, 3, 7, and 21 after paraquat treatment, TGF-β1 and collagen gene expressions, TGF-β1 protein, angiotensin-converting enzyme (ACE) activity, Ang II, and hydroxyproline contents were measured in lung tissue. Lung TGF-β1 mRNA expression progressively increased and reached a peak on day 7 after paraquat treatment. Increases in TGF-β1 mRNA expression and TGF-β1 levels preceded the onset of increased collagen I mRNA expression and hydroxyproline contents. c-myc mRNA expressions were inversely correlated with TGF-β1 protein levels in paraquat-treated lungs. Lung ACE activity decreased after paraquat administration and the decrement was maximal on day 7. Lung Ang II concentrations immediately decreased after paraquat administration and the values were not related to TGF-β1 levels. We conclude that TGF-β1 is upregulated and contribute to the paraquat-induced lung fibrosis and this effect is independent of the renin–angiotensin system.