OBJECTIVE: The focus of this study was to investigate the role of connexin (Cx) 45 in endothelial-induced mural cell differentiation. METHODS AND RESULTS: We created mural cell precursors that stably express only Cx45 in Cx43-deficient mesenchymal cells (ReCx45), and used our in vitro model of blood vessel assembly to assess the capacity of this Cx to support endothelial-induced mural cell differentiation. Lucifer Yellow dye injection and dual whole-cell patch clamping revealed that functional gap junctions exhibiting properties of Cx45-containing channels formed among ReCx45 transfectants, and between ReCx45 and endothelial cells. Heterocellular Cx45-containing gap junction channels enabled transforming growth factor-β activation and promoted the upregulation of mural cell-specific proteins in the mesenchymal precursors. CONCLUSIONS: These studies reveal a critical role for Cx45 in the regulation of endothelial-induced mural cell differentiation, which is consistent with the phenotype of Cx45-deficient embryos that exhibit dysregulated transforming growth factor-β and lack mural cell development.
OBJECTIVE: The focus of this study was to investigate the role of connexin (Cx) 45 in endothelial-induced mural cell differentiation. METHODS AND RESULTS: We created mural cell precursors that stably express only Cx45 in Cx43-deficient mesenchymal cells (ReCx45), and used our in vitro model of blood vessel assembly to assess the capacity of this Cx to support endothelial-induced mural cell differentiation. Lucifer Yellow dye injection and dual whole-cell patch clamping revealed that functional gap junctions exhibiting properties of Cx45-containing channels formed among ReCx45 transfectants, and between ReCx45 and endothelial cells. Heterocellular Cx45-containing gap junction channels enabled transforming growth factor-β activation and promoted the upregulation of mural cell-specific proteins in the mesenchymal precursors. CONCLUSIONS: These studies reveal a critical role for Cx45 in the regulation of endothelial-induced mural cell differentiation, which is consistent with the phenotype of Cx45-deficient embryos that exhibit dysregulated transforming growth factor-β and lack mural cell development.
Authors: Sarah L Dallas; Pitchumani Sivakumar; Carolyn J P Jones; Qian Chen; Donna M Peters; Deane F Mosher; Martin J Humphries; Cay M Kielty Journal: J Biol Chem Date: 2005-01-27 Impact factor: 5.157
Authors: F Cao; R Eckert; C Elfgang; J M Nitsche; S A Snyder; D F H-ulser; K Willecke; B J Nicholson Journal: J Cell Sci Date: 1998-01 Impact factor: 5.285
Authors: Laura B Payne; Huaning Zhao; Carissa C James; Jordan Darden; David McGuire; Sarah Taylor; James W Smyth; John C Chappell Journal: Microcirculation Date: 2019-05-27 Impact factor: 2.628
Authors: Peter C Stapor; Richard S Sweat; Derek C Dashti; Aline M Betancourt; Walter Lee Murfee Journal: J Vasc Res Date: 2014-05-17 Impact factor: 1.934
Authors: Erica B Peters; Nicolas Christoforou; Kam W Leong; George A Truskey; Jennifer L West Journal: Cell Mol Bioeng Date: 2015-10-20 Impact factor: 2.321
Authors: Juliann B Tefft; Jennifer L Bays; Alex Lammers; Sudong Kim; Jeroen Eyckmans; Christopher S Chen Journal: Am J Physiol Cell Physiol Date: 2021-12-08 Impact factor: 4.249