Communication between integrin receptors facilitates epicardial cell adhesion and matrix organization

Formation of the epicardium requires interactions between α₄β₁ integrin, and the extracellular matrix. We investigated the role of other integrins expressed by epicardial cells. We detected transcripts for α₅, α₈, α_v, β₁, β₃, and β₅ integrins in the chick proepicardial organ (PE). We demonstrate that α₅β₁, α ₈β₁, and α_vβ₃ integrins are expressed by chick epicardial mesothelial cells (EMCs). Migration of EMCs in vitro was reduced by RGD-containing peptides. Using adenoviruses expressing an antisense to chick α₄ (AdGFPα4AS), full-length (Adhα4V5), and C-terminal deleted α₄ (Adhα4ΔCV5), we found that EMCs were less able to adhere to vitronectin and fibronectin₁₂₀ indicating that α ₄β₁ plays a role in regulating EMC adhesion to ligands of α₅β₁, α₈β ₁, and α_vβ₃. In Adhα4Δ CV5-infected EMCs, α₅β₁ was diminished in fibrillar adhesions and new FN matrix assembly was abnormal. We propose that cooperation between α₄β₁ and RGD integrins is important for EMC adhesion and subepicardial matrix formation.