Transforming Growth Factor-ß Protein and Messenger RNA Expression Is Increased in the Closing Ductus Arteriosus

Autor: Tannenbaum, Jaime E, Waleh, Nahid S, Mauray, Françoise, Gold, Leslie, Perkett, Elizabeth A, Clyman, Ronald I
Zdroj: Pediatric Research; March 1996, Vol. 39 Issue: 3 p427-434, 8p
Abstrakt: In full-term newborns, permanent closure of the ductus arteriosus is associated with the formation of a neointima that is characterized by extracellular matrix deposition and smooth muscle cell migration. Transforming growth factor-ß (TGF-ß), a potent modulator of extracellular matrix deposition and smooth muscle cell migration, has been found to play a role in the remodeling associated with several forms of vascular disease. We examined the protein and mRNA expression of the three mammalian isoforms of TGF-ß(TGF-ß1, TGF-ß2, and TGF-ß3) during ductus arteriosus closure in full-term lambs. We found that the temporal changes and cellular localization of the proteins and mRNAs of all three TGF-ß isoforms were similar. TGF-ß proteins and mRNAs were present in very low levels in the late-gestation fetal ductus. Within 24 h of delivery, there was enhanced expression of TGF-ß in the newly forming neointima and outer muscle media; this continued to increase over the next 10 d. Increased expression of TGF-ß in the inner muscle media and adventitia lagged behind that of the neointima and outer muscle media. TGF-ß was not found in the luminal endothelial cells at any time. In contrast to the pattern described above, the appearance of TGF-ß protein differed from that of mRNA in the vasa vasorum of the ductus wall. After delivery, there was an increase in TGF-ß immunoreactivity in the smooth muscle cell layers of the vasa vasorum without any concurrent mRNA expression. The appearance of TGF-ß at the time of ductus closure suggests an important role for this growth factor in the reorganization of the ductus wall after birth.
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