Inhibition of transforming growth factor-β via the activin receptor-like kinase-5 inhibitor attenuates pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a chronic pulmonary disease that is characterized by formation of scar tissue in lungs. Transforming growth factor-β (TGF-β) is considered an important cytokine in the pathogenesis of this disease. Hence, the antifibrotic effect of an inhibitor of the TGF-β type I receptor, namely, SB 431542, was investigated in our study.

Apoptosis-dependent acute pulmonary injury after intratracheal instillation of angiotensin II.

To test the hypothesis that exogenous purified angiotensin II (ANG) might cause apoptosis of alveolar epithelial cells (AECs) and acute lung injury, male Wistar rats were intratracheally instilled with purified ANG (10 mumol/L), ANG plus the caspase inhibitor ZVAD-fmk (60 mumol/L), ANG plus the ANG receptor AT1 antagonist losartan (LOS, 100 mumol/L) or sterile phosphate-buffered saline (PBS) vehicle alone. Six or 20 h later, the lungs were lavaged in situ for determination of bronchoalveolar lavage (BAL) fluid content of hemoglobin (Hb) and fluorescent (BODIPY)-albumin, a bolus of which was injected intravenously 15 min prior to BAL. Terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) revealed that instillation of ANG, but not PBS alone, increased labeling of fragmented DNA in bronchiolar epithelial cells and in AECs (P<0.