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. 2020 Oct;55(5):724-733.
doi: 10.1111/jre.12761. Epub 2020 May 25.

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

Patricio C Smith  1 , Claudia Metz  2 , Adely de la Peña  2 , Claudia Oyanadel  2 , Patricio Avila  1 , Rodrigo Arancibia  1 , Lucas Vicuña  3 , Claudio Retamal  2 , Francisca Barake  2   4 , Alfonso González  2   4 , Andrea Soza  2   4
Affiliations

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

Patricio C Smith et al. J Periodontal Res. 2020 Oct.

Abstract

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.

Keywords: fibrosis; focal adhesion kinase 1; galectins; gingival overgrowth; integrins.

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References

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