The mechanism of transforming growth factor beta1 in myofibroblast differentiation / 中华外科杂志
Chinese Journal of Surgery
; (12): 986-989, 2007.
Article
em Zh
| WPRIM
| ID: wpr-340875
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanism underlying myofibroblast differentiation induced by transforming growth factor (TGF) beta1 in obliterative bronchiolitis following lung transplantation.</p><p><b>METHODS</b>Heterotopic tracheal transplantation was performed in Smad3 wild-type and knock-out mice to simulate the lung transplantation in human. Murine tracheal fibroblasts cultivated in primary culture were used for in vitro study. Immunohistochemistry, immunocytochemistry, Western Blotting, RT-PCR and DNA electrophoresis mobility gel shift assay were conducted to detect the expression of alpha-smooth muscle actin (alphaSMA), the marker of fibroblast-myofibroblast differentiation, and the activation of Smad3, p38 and ERK1/2.</p><p><b>RESULTS</b>In affected airways of experimental obliterative bronchiolitis, abundant expression of alphaSMA were found. In vitro study for tracheal fibroblasts, the activation of Smad3 by TGF-beta1 presents as three major forms, phosphorylation, nuclear translocation and DNA binding. In Smad3 wild-type fibroblasts, TGF-beta1 induces the increase of the myofibroblasts transformation, characterized by the elevation of alphaSMA, both at transcription and protein level. While in Smad3 knock-out fibroblasts, the transformation of myofibroblasts induced by TGF-beta1 is significantly decreased (t = 2.080, P = 0.027; t = 1.982, P = 0.032), but not completely abolished. Further study in Smad3-deficient fibroblasts demonstrates that p38 and ERK1/2 could be activated by TGF-beta1 and result in fibroblast differentiation.</p><p><b>CONCLUSIONS</b>TGF-beta1 could promote the transformation of fibroblasts into myofibroblasts in Smad3 dependent and independent signal pathways, especially the Smad3 dependent path, and result in the development of obliterative bronchiolitis.</p>
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Índice:
WPRIM
Assunto principal:
Patologia
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Farmacologia
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Cirurgia Geral
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Traqueia
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Transplante
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Bronquiolite Obliterante
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Imuno-Histoquímica
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Diferenciação Celular
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Células Cultivadas
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Western Blotting
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
Zh
Revista:
Chinese Journal of Surgery
Ano de publicação:
2007
Tipo de documento:
Article