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Transforming Growth Factor-1 Induces Trans differentiation of Fibroblasts into Myofibroblasts in Hypoxic Pulmonary Vascular Remodeling

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Abstract

The muscularization of non-muscular pulmonary arterioles is an important pathological feature of hypoxic pulmonary vascular remodeling. However, the origin of the cells involved in this process is still not well understood. The present study was undertaken to test the hypothesis that transforming growth factor-1 (TGF-1) can induce transdifferentiation of fibroblasts into myofibroblasts, which might play a key role in the muscularization of non-muscular pulmonary arterioles. It was found that mean pulmonary arterial pressure increased significantly after 7 d of hypoxia. Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d of hypoxia. The distribution of nonmuscular, partially muscular, and muscular vessels was significantly different after 7 d of hypoxia. Immunocytochemistry results demonstrated that the expression of -smooth muscle actin was increased in intra-acinar pulmonary arteries with increasing hypoxic time. TGF-1 mRNA expression in pulmonary arterial walls was increased significantly after 14 d of hypoxia, but showed no obvious changes after 3 or 7 d of hypoxia. In pulmonary tunica adventitia and tunica media, TGF-1 protein staining was poorly positive in control rats, but was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia. The myofibroblast phenotype was confirmed by electron microscopy, which revealed microfilaments and a well-developed rough endoplasmic reticulum. Taken together, our results suggested that TGF-1 induces transdifferentiation of fibroblasts into myofibroblasts, which is important in hypoxic pulmonary vascular remodeling.

Edited by

Ming-Hua XU
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Keywords: fibroblast; hypertension; lung; myofibroblast; transforming growth factor-1

Document Type: Research Article

Affiliations: Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha 410001, China

Publication date: 01 January 2006

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