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The Canonical Wnt Signaling Pathway Inhibits the Glucocorticoid Receptor Signaling Pathway in the Trabecular Meshwork.
Sugali, Chenna Kesavulu; Rayana, Naga Pradeep; Dai, Jiannong; Peng, Michael; Harris, Sherri L; Webber, Hannah C; Liu, Shaohui; Dixon, Stephan G; Parekh, Priyanka H; Martin, Elizabeth A; Cantor, Louis B; Fellman, Ronald L; Godfrey, David G; Butler, Michelle R; Emanuel, Matthew E; Grover, Davinder S; Smith, Oluwatosin U; Clark, Abbot F; Raghunathan, Vijay Krishna; Mao, Weiming.
Afiliación
  • Sugali CK; Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana.
  • Rayana NP; Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana.
  • Dai J; Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana.
  • Peng M; Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana.
  • Harris SL; Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas.
  • Webber HC; Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas.
  • Liu S; Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana.
  • Dixon SG; Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana.
  • Parekh PH; Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana.
  • Martin EA; Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana.
  • Cantor LB; Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana.
  • Fellman RL; Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas; Glaucoma Associates of Texas, Dallas, Texas.
  • Godfrey DG; Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas; Glaucoma Associates of Texas, Dallas, Texas.
  • Butler MR; Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas; Glaucoma Associates of Texas, Dallas, Texas.
  • Emanuel ME; Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas; Glaucoma Associates of Texas, Dallas, Texas.
  • Grover DS; Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas; Glaucoma Associates of Texas, Dallas, Texas.
  • Smith OU; Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas; Glaucoma Associates of Texas, Dallas, Texas.
  • Clark AF; Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas.
  • Raghunathan VK; Department of Basic Sciences, College of Optometry, University of Houston, Houston, Texas.
  • Mao W; Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: weimmao@iu.edu.
Am J Pathol ; 191(6): 1020-1035, 2021 06.
Article en En | MEDLINE | ID: mdl-33705750
Glucocorticoid-induced glaucoma is a secondary open-angle glaucoma. About 40% of the general population may develop elevated intraocular pressure on prolonged glucocorticoid treatment secondary to damages in the trabecular meshwork (TM), a tissue that regulates intraocular pressure. Therefore, identifying the key molecules responsible for glucocorticoid-induced ocular hypertension is crucial. In this study, Dickkopf-related protein 1 (Dkk1), a canonical Wnt signaling inhibitor, was found to be elevated in the aqueous humor and TM of glaucoma patients. At the signaling level, Dkk1 enhanced glucocorticoid receptor (GR) signaling, whereas Dkk1 knockdown or Wnt signaling activators decreased GR signaling in human TM cells as indicated by luciferase assays. Similarly, activation of the GR signaling inhibited Wnt signaling. At the protein level, glucocorticoid-induced extracellular matrix was inhibited by Wnt activation using Wnt activators or Dkk1 knockdown in primary human TM cells. In contrast, inhibition of canonical Wnt signaling by ß-catenin knockdown increased glucocorticoid-induced extracellular matrix proteins. At the physiological level, adenovirus-mediated Wnt3a expression decreased glucocorticoid-induced ocular hypertension in mouse eyes. In summary, Wnt and GR signaling inhibit each other in the TM, and canonical Wnt signaling activators may prevent the adverse effect of glucocorticoids in the eye.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Malla Trabecular / Receptores de Glucocorticoides / Glaucoma / Vía de Señalización Wnt Límite: Animals / Female / Humans Idioma: En Revista: Am J Pathol Año: 2021 Tipo del documento: Article 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: Malla Trabecular / Receptores de Glucocorticoides / Glaucoma / Vía de Señalización Wnt Límite: Animals / Female / Humans Idioma: En Revista: Am J Pathol Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos