BMP ligand-receptor interactions contribute to experimental tracheoesophageal fistula

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• 作者：Troy Spilde ; Am ; a Crowley ; Sheilendra Mehta ; Daniel Ostlie ; Krishna Prasadan ; Mark Hembree ; Barry Preuett ; Sidhartha Tulachan ; George W. Holcomb III ; George Gittes ; Charles Snyder
• 刊名：Journal of the American College of Surgeons
• 出版年：2004
• 出版时间：September 2004
• 年：2004
• 卷：199
• 期：3, Supplement 1
• 页码：30
• 全文大小：51 K

文摘

Introduction: The mechanism of formation of esophageal atresia with tracheoesophageal fistula (EA/TEF) remains unclear. Previously, we demonstrated that the fistula tract develops from a trifurcation of the embryonic lung bud. The fistula tract then grows caudally without branching, unlike the bronchi, which branch normally. Bone Morphogenetic Protein (BMP) signaling is critical to lung branching. We hypothesized that defects in BMP signaling may be causative in EA/TEF.

Methods: Adriamycin was administered to pregnant rats to induce TEF. Foregut microdissection was performed at E13 and E17. Tissues were analyzed using immunohistochemistry for BMP ligands (BMP2, BMP4, BMP7) and receptors (BMPRIA, BMPRIB, BMPRII).

Results: All three BMP ligands were present at E13, specifically on the luminal side of the esophageal mucosa, but not in fistula or lung. By E17 the ligands were present in the mucosa of esophagus and fistula, but remained absent in lung. At E17 all BMP receptors also were localized to only the luminal surface of esophagus and fistula. In lung, only BMPRII was present.

Conclusions: Proper BMP signaling necessitates heterodimerization of type II receptor and type I receptors. Heterodimerization appears feasible in both fistula tract and esophagus at E17, but not in lung, where the type I receptor is absent. In addition, early intestinalization of the lung bud in the region of the fistula is possible because both type I and type II receptors are present on the luminal surface with BMP ligands locally.