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Discoidin domain receptor 2 regulates aberrant mesenchymal lineage cell fate and matrix organization.
Pagani, Chase A; Bancroft, Alec C; Tower, Robert J; Livingston, Nicholas; Sun, Yuxiao; Hong, Jonathan Y; Kent, Robert N; Strong, Amy L; Nunez, Johanna H; Medrano, Jessica Marie R; Patel, Nicole; Nanes, Benjamin A; Dean, Kevin M; Li, Zhao; Ge, Chunxi; Baker, Brendon M; James, Aaron W; Weiss, Stephen J; Franceschi, Renny T; Levi, Benjamin.
Afiliación
  • Pagani CA; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
  • Bancroft AC; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
  • Tower RJ; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
  • Livingston N; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
  • Sun Y; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
  • Hong JY; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
  • Kent RN; Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Strong AL; Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Nunez JH; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
  • Medrano JMR; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.
  • Patel N; Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Nanes BA; Department of Dermatology, University of Texas Southwestern, Dallas, TX, USA.
  • Dean KM; Lydia Hill Department of Bioinformatics, University of Texas Southwestern, Dallas, TX, USA.
  • Li Z; Lydia Hill Department of Bioinformatics, University of Texas Southwestern, Dallas, TX, USA.
  • Ge C; Cecil H. and The Ida Green Center for Systems Biology, University of Texas Southwestern, Dallas, TX, USA.
  • Baker BM; Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
  • James AW; School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
  • Weiss SJ; Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Franceschi RT; Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
  • Levi B; Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Sci Adv ; 8(51): eabq6152, 2022 12 21.
Article en En | MEDLINE | ID: mdl-36542719
Extracellular matrix (ECM) interactions regulate both the cell transcriptome and proteome, thereby determining cell fate. Traumatic heterotopic ossification (HO) is a disorder characterized by aberrant mesenchymal lineage (MLin) cell differentiation, forming bone within soft tissues of the musculoskeletal system following traumatic injury. Recent work has shown that HO is influenced by ECM-MLin cell receptor signaling, but how ECM binding affects cellular outcomes remains unclear. Using time course transcriptomic and proteomic analyses, we identified discoidin domain receptor 2 (DDR2), a cell surface receptor for fibrillar collagen, as a key MLin cell regulator in HO formation. Inhibition of DDR2 signaling, through either constitutive or conditional Ddr2 deletion or pharmaceutical inhibition, reduced HO formation in mice. Mechanistically, DDR2 perturbation alters focal adhesion orientation and subsequent matrix organization, modulating Focal Adhesion Kinase (FAK) and Yes1 Associated Transcriptional Regulator and WW Domain Containing Transcription Regulator 1 (YAP/TAZ)-mediated MLin cell signaling. Hence, ECM-DDR2 interactions are critical in driving HO and could serve as a previously unknown therapeutic target for treating this disease process.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor con Dominio Discoidina 2 Límite: Animals Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor con Dominio Discoidina 2 Límite: Animals Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos