title: Transglutaminase 2 expression is significantly increased in cyclosporine-induced gingival overgrowth.
abstract: Cyclosporine A is a potent immunosuppressant used to prevent organ transplant rejection and treat various autoimmune diseases. However, cyclosporine A can also induce gingival overgrowth, which is characterized by increased extracellular matrix due to an altered balance between collagen synthesis and degradation. This study proposed to verify whether trans-glutaminase 2, an enzyme thought to be responsible for the assembly and remodelling of extracellular matrix, plays any role in the pathogenesis of cyclosporine A-induced gingival overgrowth. Cyclosporine A-induced gingival overgrowths were collected from 21 liver transplant patients and case-controlled with 20 non-hyperplastic gingival biopsies from healthy patients who had previous periodontal treatment. In both groups, the presence and tissue distribution of transglutaminase 2 were determined by immunohistochemistry and analyzed in comparison with the tissue morphology and expression of lymphocyte-related antigens (CD3 and CD20) and a vessel-related marker (CD34). Transglutaminase 2 expression showed a significant increase (2.6-fold) in the stromal component of cyclosporine A-treated patients compared with controls (p<0.001), which suggested that transglutaminase 2 had a role in the pathogenesis of the disease. Further studies should investigate the therapeutic effect of anti-transglutaminase 2 drugs (putrescine or 1,4-diamino-butane) in these patients.
authors.affiliation: Department of Biomedical Sciences and Human Oncology, University of Turin, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Asioli
authors.forename: A
authors.initials: A
authors.lastname: Righi
authors.forename: P
authors.initials: P
authors.lastname: Cardone
authors.forename: M
authors.initials: M
authors.lastname: Aimetti
authors.forename: F
authors.initials: F
authors.lastname: Maletta
authors.forename: R
authors.initials: R
authors.lastname: Coda
authors.forename: S
authors.initials: S
authors.lastname: Carossa
authors.forename: R
authors.initials: R
authors.lastname: Navone
authors.forename: P
authors.initials: P
authors.lastname: Cassoni
mesh_terms: D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D019214:Gingival Overgrowth / Q000139:chemically induced* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins