title: Cadherin-11 regulates both mesenchymal stem cell differentiation into smooth muscle cells and the development of contractile function in vivo.
abstract: Although soluble factors, such as transforming growth factor β1 (TGF-β1), induce mesenchymal stem cell (MSC) differentiation towards the smooth muscle cell (SMC) lineage, the role of adherens junctions in this process is not well understood. In this study, we found that cadherin-11 but not cadherin-2 was necessary for MSC differentiation into SMCs. Cadherin-11 regulated the expression of TGF-β1 and affected SMC differentiation through a pathway that was dependent on TGF-β receptor II (TGFβRII) but independent of SMAD2 or SMAD3. In addition, cadherin-11 activated the expression of serum response factor (SRF) and SMC proteins through the Rho-associated protein kinase (ROCK) pathway. Engagement of cadherin-11 increased its own expression through SRF, indicative of the presence of an autoregulatory feedback loop that committed MSCs to the SMC fate. Notably, SMC-containing tissues (such as aorta and bladder) from cadherin-11-null (Cdh11(-/-)) mice showed significantly reduced levels of SMC proteins and exhibited diminished contractility compared with controls. This is the first report implicating cadherin-11 in SMC differentiation and contractile function in vitro as well as in vivo.
authors.affiliation: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, NY 14260-4200, USA.
authors.forename: Stella
authors.initials: S
authors.lastname: Alimperti
authors.affiliation: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, NY 14260-4200, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: You
authors.affiliation: Baylor College of Medicine, Department of Medicine, Section of Allergy, Immunology, and Rheumatology, Biology of Inflammation Center, One Baylor Plaza, Suite 672E, MS, BCM285, Houston, TX 77030, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: George
authors.affiliation: Baylor College of Medicine, Department of Medicine, Section of Allergy, Immunology, and Rheumatology, Biology of Inflammation Center, One Baylor Plaza, Suite 672E, MS, BCM285, Houston, TX 77030, USA.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Agarwal
authors.affiliation: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, NY 14260-4200, USA Department of Biomedical Engineering, University at Buffalo, The State University of New York, Amherst, NY 14260-4200, USA Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY 14203, USA sandread@buffalo.edu.
authors.forename: Stelios T
authors.initials: ST
authors.lastname: Andreadis
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D004789:Enzyme Activation; D025461:Feedback, Physiological; D015870:Gene Expression; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D001743:Urinary Bladder / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D015820:Cadherins; C489083:Cdh2 protein, mouse; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; C086960:osteoblast cadherin; D054460:rho-Associated Kinases
keywords: Adherens junctions; Cell–cell adhesion; Differentiation; Mesenchymal stem cells; Smooth muscle cells; Vascular contractility
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