Autophagy activation is required for myofibroblast differentiation during healing of oral mucosa

Aim: It is known that periodontal tissues heal faster that skin, and gingiva in particular heal without scar formation. The mechanisms regulating this behaviour are still unclear. The aim of our work was to compare wound healing in oral mucosa and gingiva, investigating the role of α-smooth muscle actin (αSMA)-expressing myofibroblasts and autophagy. Materials and Methods: Biopsies were obtained from seven patients immediately before and 24 hr after vertical releasing incision in oral mucosa and attached gingiva. Both whole biopsies and primary cultures of fibroblasts derived from the same tissues were subjected to immunofluorescence, Western blot and quantitative real-time PCR analyses. Results: We demonstrated that in oral mucosa, characterized by partially fibrotic outcome during repair, the activation of autophagy determined an increase in αSMA and collagen 1a1 production. Conversely, wound healing did not stimulate autophagy in attached gingiva, and subsequently, no increase in myofibroblast differentiation and collagen deposition could be seen, thus justifying its scarless outcome. Conclusions: The elucidation of the differential regulation of autophagy in periodontal tissues and its correlation with myofibroblast differentiation and fibrotic outcome could allow the identification of new molecules involved in periodontal healing and the development of new surgical approaches for periodontal treatment that could improve the outcome of postoperative wounds