title: TGFβ signaling promotes matrix assembly during mechanosensitive embryonic salivary gland restoration.
abstract: Mechanical properties of the microenvironment regulate cell morphology and differentiation within complex organs. However, methods to restore morphogenesis and differentiation in organs in which compliance is suboptimal are poorly understood. We used mechanosensitive mouse salivary gland organ explants grown at different compliance levels together with deoxycholate extraction and immunocytochemistry of the intact, assembled matrices to examine the compliance-dependent assembly and distribution of the extracellular matrix and basement membrane in explants grown at permissive or non-permissive compliance. Extracellular matrix and basement membrane assembly were disrupted in the glands grown at low compliance compared to those grown at high compliance, correlating with defective morphogenesis and decreased myoepithelial cell differentiation. Extracellular matrix and basement membrane assembly as well as myoepithelial differentiation were restored by addition of TGFβ1 and by mechanical rescue, and mechanical rescue was prevented by inhibition of TGFβ signaling during the rescue. We detected a basal accumulation of active integrin β1 in the differentiating myoepithelial cells that formed a continuous peripheral localization around the proacini and in clefts within active sites of morphogenesis in explants that were grown at high compliance. The pattern and levels of integrin β1 activation together with myoepithelial differentiation were interrupted in explants grown at low compliance but were restored upon mechanical rescue or with application of exogenous TGFβ1. These data suggest that therapeutic application of TGFβ1 to tissues disrupted by mechanical signaling should be examined as a method to promote organ remodeling and regeneration.
authors: Department of Biological Sciences, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.
authors: Sarah B
authors: SB
authors: Peters
authors: Department of Biological Sciences, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States.
authors: Deirdre A
authors: DA
authors: Nelson
authors: Department of Biological Sciences, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States; Graduate Program in Molecular, Cellular, Neural, and Developmental Biology, University at Albany, State University of New York, United States.
authors: Hae Ryong
authors: HR
authors: Kwon
authors: Department of Biological Sciences, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States; Graduate Program in Molecular, Cellular, Neural, and Developmental Biology, University at Albany, State University of New York, United States.
authors: Matthew
authors: M
authors: Koslow
authors: Department of Biological Sciences, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States; Graduate Program in Molecular, Cellular, Neural, and Developmental Biology, University at Albany, State University of New York, United States.
authors: Kara A
authors: KA
authors: DeSantis
authors: Department of Biological Sciences, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, United States. Electronic address: mlarsen@albany.edu.
authors: Melinda
authors: M
authors: Larsen
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000187:drug effects; D001696:Biomechanical Phenomena; D002454:Cell Differentiation / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects*; D005260:Female; D019012:Integrin beta1 / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects*; D009924:Organ Culture Techniques; D011247:Pregnancy; D012469:Salivary Glands / Q000166:cytology / Q000196:embryology / Q000254:growth & development*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D019012:Integrin beta1; D016212:Transforming Growth Factor beta
keywords: Basement membrane; Branching morphogenesis; Compliance; Extracellular matrix; Integrin beta 1; Organogenesis; Salivary gland; Transforming growth factor beta
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