Korean J Pathol.
1999 Aug;33(8):545-554.
Expression of TGF-beta and PDGF in Monocrotaline-Induced Pulmonary Hypertension in Rats
- Affiliations
-
- 1Department of Pathology, Yonsei University College of Medicine, Korea.
- 2Department of Pathology, Ewha Womans University College of Medicine, Seoul 158-710, Korea.
Abstract
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Pulmonary vascular hypertension is characterized by migration and proliferation of
smooth muscle cells accompanying abnormal synthesis and accumulation of extracellular
proteins in vascular wall. The aim of this study is to define the role of endogneous
TGF-betas and PDGF in the process of remodeling vessels through determining the
temporal and spatial distribution of these growth factors in hypertensive pulmonary
vessels in monocrotaline-induced pulmonary hypertension in rat. Sprague-Dawley rats
were sacrificed 12 hours, 1, 2, 4, 7, 10, 14, 21, 28, and 56 days after treatment. The
morphometric analysis of medial thickening and immunohistochemical study using
antibodies to TGF-beta1, TGF-beta2, TGF-beta3, and PDGF were performed.
Immunoreactivities for TGF-beta1 and TGF-beta3 were increased from the 14th day in the
medial smooth muscle cells and PDGF showed increased expression from the 21st day
in the medial smooth muscle cells. No difference in TGF-beta2 immunoreactivity was
found between control and experimental groups. The expression of TGF-beta1, TGF-beta3
and PDGF increased in medial layers with the progressive thickening of pulmonary
arteries which was considered to have close relation to medial hypertrophy of pulmonary
arterioles. In the case of PDGF, however, the morphologic change occurred before
increase in immunoreactivity was observed in the medial layer of pulmonary arterioles.
Moreover, the function of isoforms of TGF-beta has yet to be completely elucidated; the
different affinity to receptors and the degree of expression of these receptors that are
supposed to affect the function of growth factors. Thus, further studies are needed.