Expression of transforming growth factor-beta mRNAs and proteins in pulmonary vascular remodeling in the sheep air embolization model of pulmonary hypertension.

Transforming growth factor-beta (TGF-beta) has been suggested as one of the mediators of vascular remodeling in chronic pulmonary hypertension. We have previously shown a transient early increase in TGF-beta levels in lung lymph during the development of sustained pulmonary hypertension in a sheep model (12 days of air embolization). The present study examines expression and cellular localization of mRNA and protein of the three mammalian isoforms of TGF-beta in lung biopsy tissue taken during the development of pulmonary hypertension (0, 1, 4, 8, and 12 days of embolization). In control tissue, immunohistochemical techniques localized each of the TGF-beta proteins in an identical pattern in large preacinar airways--bronchial epithelium and subepithelial cells--and in the medial wall of muscular vessels; no protein was detected in intraacinar regions. Following air embolization, immunoreactivity appeared in peripheral lung. At day 1, immunoreactivity for TGF-beta 1 and TGF-beta 3 proteins was seen in edema fluid, in perivascular cells associated with nonmuscular intraacinar arteries, and in alveolar walls; no increased immunoreactivity was detected for TGF-beta 2. After 4, 8, and 12 days of embolization, immunoreactivity for all three TGF-beta proteins was associated with newly muscularized intraacinar arteries. With in situ hybridization, the three TGF-beta mRNAs co-localized in lung tissue from both control and air-embolized animals. In control tissue, hybridization was seen around preacinar airways and muscular vessels; no hybridization seen in intraacinar regions of the lung. After 1 day of embolization, the pattern of hybridization was similar to controls.(ABSTRACT TRUNCATED AT 250 WORDS)