Clarification of control mechanism in lung and bronchial by Wnt signaling

2015 Fiscal Year Final Research Report

• Project/Area Number: 25861669
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Research Institute, Osaka Medical Center for Maternal and Child Health (2015); Osaka University (2013-2014)
• Principal Investigator: IBUKA SOUJI 地方独立行政法人大阪府立病院機構大阪府立母子保健総合医療センター(研究所), その他部局等, 小児外科・診療主任 (50625027)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: P2Y2R / 上皮管腔形成 / インテグリン / フィブロネクチン / Wnt / EGF

Outline of Final Research Achievements

We used rat intestinal epithelial IEC6 cells to investigate tubulogenesis and we found that tubular formation was induced by a combination of Wnt3a and EGF signaling during 3D culture. Wnt3a and EGF induced the expression of the P2Y2 receptor, and knockdown of P2Y2R suppressed tubular formation. The Arg-Gly-Asp (RGD) sequence of P2Y2R has been shown to interact with integrins, and a P2Y2R mutant lacking integrin-binding activity was unable to induce tubular formation. P2Y2R expression inhibited the interaction between integrins and fibronectin. Inhibition of integrin and fibronectin binding by treatment with the cyclic RGD peptide and fibronectin knockdown induced tubular formation in the presence of EGF alone, but a fibronectin coat suppressed Wnt3a- and EGF-induced tubular formation. These results suggest that Wnt3a- and EGF-induced P2Y2R expression causes tubular formation by preventing the binding of integrins and fibronectin rather than by mediating nucleotide responses.

Free Research Field

小児外科