Your browser doesn't support javascript.
loading
The Hippo signaling pathway effector YAP promotes salivary gland regeneration after injury.
Rocchi, Cecilia; Cinat, Davide; Serrano Martinez, Paola; Bruin, Anne L Jellema-de; Baanstra, Mirjam; Brouwer, Uilke; Del Angel Zuivre, Cinthya; Schepers, Hein; van Os, Ronald; Barazzuol, Lara; Coppes, Robert P.
Afiliación
  • Rocchi C; Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen 9713 AV, Netherlands.
  • Cinat D; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen 9700 RB, Netherlands.
  • Serrano Martinez P; Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen 9713 AV, Netherlands.
  • Bruin ALJ; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen 9700 RB, Netherlands.
  • Baanstra M; Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen 9713 AV, Netherlands.
  • Brouwer U; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen 9700 RB, Netherlands.
  • Del Angel Zuivre C; Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen 9713 AV, Netherlands.
  • Schepers H; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen 9700 RB, Netherlands.
  • van Os R; Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen 9713 AV, Netherlands.
  • Barazzuol L; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen 9700 RB, Netherlands.
  • Coppes RP; Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen 9713 AV, Netherlands.
Sci Signal ; 14(712): eabk0599, 2021 Dec 07.
Article en En | MEDLINE | ID: mdl-34874744
Salivary glands are damaged by radiotherapy for head and neck cancers, which often culminates in radiation-induced hyposalivation and xerostomia that may be permanent. Here, we identified a central role for YAP in the regenerative response of the salivary gland. Activation of the Hippo signaling pathway inhibits the phosphorylation of YAP, leading to its nuclear translocation and transcriptional activity. Using mice with salivary gland injury induced by surgical ligation and salivary gland­derived organoids, we found that YAP nuclear localization in the salivary gland epithelium changed dynamically between homeostasis and regeneration. Whereas local injury had no effect on nuclear YAP localization in saliva-producing acinar cells, it triggered nuclear accumulation of YAP in saliva-transporting ductal cells. Injury also stimulated the proliferation of ductal cells, which were mainly quiescent under homeostatic conditions and in nonregenerating areas distal to the injury site, thus enabling salivary gland regeneration. Overexpressing YAP or driving YAP nuclear translocation by inhibiting upstream Hippo pathway kinases increased the capacity of mouse and human salivary gland cells, including human cells that had been irradiated, to form lobed organoids in vitro. Our results identify a YAP-driven regeneration program in salivary gland ductal cells that could be used to promote salivary gland regeneration after irradiation-induced damage.
Asunto(s)
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: Proteínas Serina-Treonina Quinasas / Proteínas Adaptadoras Transductoras de Señales Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: 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: Proteínas Serina-Treonina Quinasas / Proteínas Adaptadoras Transductoras de Señales Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos