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The role of the type III transforming growth factor‐β receptor Tgfbr3 in the regulation of pulmonary vascular development
Author(s) -
Niess Gero,
Wygowski Jegor,
Seeger Werner,
Morty Rory Edward
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1141.2
Subject(s) - transforming growth factor , gene knockdown , lung , biology , vascular smooth muscle , receptor , pulmonary artery , endocrinology , medicine , transforming growth factor beta , pathology , apoptosis , smooth muscle , biochemistry
Bronchopulmonary dysplasia (BPD) is associated with poor alveolar and vascular development. The molecular basis of this is not well understood. Expression studies in the lung of hyperoxia (85% O2) treated mice, a model of BPD, have revealed that the protein level of the type III TGF‐β receptor (Tgfbr3) is reduced by 4‐fold. Laser microdissection confirmed downregulated expression (mRNA level) of tgfbr3 in the pulmonary vasculature of the developing mouse lung. Immunohistochemical studies suggested that the changes in TGF‐β receptor expression were largely confined to the pulmonary vascular smooth muscle, suggesting a possible role for these receptors in the smooth muscle tissue in the development of BPD. Knockdown of TGFBR3 in primary pulmonary artery smooth muscle cells (PASMC) increased proliferation by 2‐fold, in a TGF‐β‐independent manner (observed in the presence of the TGF‐β pathway inhibitor SB431542). Migration of PASMC assessed by Boyden Assay was increased 4‐fold. However, apoptosis of PASMC was not affected by the knockdown of TGFBR3. Taken together, these data suggest a role for TGFBR3 in vascular smooth muscle cell function which could lead to a dysregulation of TGF‐β signalling in the pulmonary vasculature which in turn could contribute to the impaired pulmonary vascular growth and development associated with the lung hypoplasia observed in patients with BPD. German research foundation.