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Actin Polymerization Status Regulates Tendon Homeostasis through Myocardin-Related Transcription Factor-A.
West, Valerie C; Owen, Kaelyn; Inguito, Kameron L; Ebron, Karl Matthew M; Reiner, Tori; Mirack, Chloe E; Le, Christian; de Cassia Marqueti, Rita; Snipes, Steven; Mousavizadeh, Rouhollah; Elliott, Dawn M; Parreno, Justin.
Afiliación
  • West VC; Department of Biomedical Engineering, University of Delaware, Newark, DE, USA.
  • Owen K; Department of Biomedical Engineering, University of Delaware, Newark, DE, USA.
  • Inguito KL; Department of Biological Sciences, University of Delaware, Newark, DE, USA.
  • Ebron KMM; Department of Kinesiology and Applied Physiology, University of DE, USA.
  • Reiner T; Department of Biological Sciences, University of Delaware, Newark, DE, USA.
  • Mirack CE; Department of Biological Sciences, University of Delaware, Newark, DE, USA.
  • Le C; Department of Biomedical Engineering, University of Delaware, Newark, DE, USA.
  • de Cassia Marqueti R; Laboratory of Molecular Analysis, Graduate Program of Rehabilitation Sciences, University of Brasília, Brasília, Distrito Federal, Brazil.
  • Snipes S; Department of Biological Sciences, University of Delaware, Newark, DE, USA.
  • Mousavizadeh R; Department of Physical Therapy, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
  • Elliott DM; Department of Biomedical Engineering, University of Delaware, Newark, DE, USA.
  • Parreno J; Department of Biomedical Engineering, University of Delaware, Newark, DE, USA.
bioRxiv ; 2024 Aug 26.
Article en En | MEDLINE | ID: mdl-39253450
ABSTRACT
The actin cytoskeleton is a potent regulator of tenocyte homeostasis. However, the mechanisms by which actin regulates tendon homeostasis are not entirely known. This study examined the regulation of tenocyte molecule expression by actin polymerization via the globular (G-) actin-binding transcription factor, myocardin-related transcription factor-a (MRTF). We determined that decreasing the proportion of G-actin in tenocytes by treatment with TGFß1 increases nuclear MRTF. These alterations in actin polymerization and MRTF localization coincided with favorable alterations to tenocyte gene expression. In contrast, latrunculin A increases the proportion of G-actin in tenocytes and reduces nuclear MRTF, causing cells to acquire a tendinosis-like phenotype. To parse out the effects of F-actin depolymerization from regulation by MRTF, we treated tenocytes with cytochalasin D. Similar to latrunculin A treatment, exposure of cells to cytochalasin D increases the proportion of G-actin in tenocytes. However, unlike latrunculin A treatment, cytochalasin D increases nuclear MRTF. Compared to latrunculin A treatment, cytochalasin D led to opposing effects on the expression of a subset of genes. The differential regulation of genes by latrunculin A and cytochalasin D suggests that actin signals through MRTF to regulate a specific subset of genes. By targeting the deactivation of MRTF through the inhibitor CCG1423, we verify that MRTF regulates Type I Collagen, Tenascin C, Scleraxis, and α-smooth muscle actin in tenocytes. Actin polymerization status is a potent regulator of tenocyte homeostasis through the modulation of several downstream pathways, including MRTF. Understanding the regulation of tenocyte homeostasis by actin may lead to new therapeutic interventions against tendinopathies, such as tendinosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos