Galectin-8 mediates fibrogenesis induced by cyclosporine in human gingival fibroblasts

Patricio C. Smith, Claudia Metz, Adely de la Peña, Claudia Oyanadel, Patricio Avila, Rodrigo Arancibia, Lucas Vicuña, Claudio Retamal, Francisca Barake, Alfonso González*, Andrea Soza*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

5 Citas (Scopus)


Background and Objective: During cyclosporine-induced gingival overgrowth, the homeostatic balance of gingival connective tissue is disrupted leading to fibrosis. Galectins are glycan-binding proteins that can modulate a variety of cellular processes including fibrosis in several organs. Here, we study the role of galectin-8 (Gal-8) in the response of gingival connective tissue cells to cyclosporine. Methods: We used human gingival fibroblasts and mouse NIH3T3 cells treated with recombinant Gal-8 and/or cyclosporine for analyzing specific mRNA and protein levels through immunoblot, real-time polymerase chain reaction, ELISA and immunofluorescence, pull-down with Gal-8-Sepharose for Gal-8-to-cell surface glycoprotein interactions, short hairpin RNA for Gal-8 silencing and Student's t test and ANOVA for statistical analysis. Results: Galectin-8 stimulated type I collagen and fibronectin protein levels and potentiated CTGF protein levels in TGF-β1-stimulated human gingival fibroblasts. Gal-8 interacted with α5β1-integrin and type II TGF-β receptor. Gal-8 stimulated fibronectin protein and mRNA levels, and this response was dependent on FAK activity but not Smad2/3 signaling. Cyclosporine and tumor necrosis factor alpha (TNF-α) increased Gal-8 protein levels. Finally, silencing of galectin-8 in NIH3T3 cells abolished cyclosporine-induced fibronectin protein levels. Conclusion: Taken together, these results reveal for the first time Gal-8 as a fibrogenic stimulus exerted through β1-integrin/FAK pathways in human gingival fibroblasts, which can be triggered by cyclosporine. Further studies should explore the involvement of Gal-8 in human gingival tissues and its role in drug-induced gingival overgrowth.

Idioma originalInglés
Páginas (desde-hasta)724-733
Número de páginas10
PublicaciónJournal of Periodontal Research
EstadoPublicada - 2020

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Publisher Copyright:
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Áreas temáticas de ASJC Scopus

  • Parodontología


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