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

Smith, Patricio C.; Metz, Claudia.; de la Pena, Adely; Oyanadel, Claudia; Avila, Patricio; Arancibia, Rodrigo; Vicuna, Lucas; Retamal, Claudio; Barake, Francisca; Gonzalez, Alfonso; Soza, Andrea


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-beta 1-stimulated human gingival fibroblasts. Gal-8 interacted with alpha 5 beta 1-integrin and type II TGF-beta 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-alpha) 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 beta 1-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.

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Título según WOS: ID WOS:000535069900001 Not found in local WOS DB
Editorial: Wiley
Fecha de publicación: 2020


Notas: ISI