title: Down-regulation of Smad3 accelerates palatal wound repair.
abstract: Smad3-deficient mice exhibit accelerated re-epithelialization and tissue remodeling during palatal wound repair. In addition, transforming growth factor beta 1 (TGF-β1) and other inflammatory factors are down-regulated compared with those in wild-type mice. The aim of this study was to examine whether targeting of Smad3 with small interfering RNA (siRNA) accelerates wound-healing and inhibits wound contraction in palatal mucoperiosteal wounds. An initial histological examination of wound closure in mouse palates treated with Smad3-targeted siRNA vs. a scrambled siRNA found that wound-healing was accelerated when levels of Smad3 were decreased. Furthermore, with real-time PCR, mRNA levels of Smad3, TGF-β1, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) were found to be significantly down-regulated in palatal tissue treated with Smad3-targeted siRNA vs. a control siRNA. Protein and mRNA levels of α-smooth-muscle actin (α-SMA), type I collagen, and fibronectin were also lower in palates treated with Smad3-targeted siRNA vs. control siRNA. Taken together, these results indicate that down-regulation of Smad3 expression by siRNA can accelerate wound-healing and may inhibit wound contraction. Therefore, siRNA-targeted inhibition of Smad3 may represent a valuable therapeutic tool for palatal mucoperiosteal wound-healing.
authors.affiliation: Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yoneda
authors.forename: A
authors.initials: A
authors.lastname: Yasue
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: E
authors.initials: E
authors.lastname: Tanaka
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis; D054405:Chemokine CCL3 / Q000032:analysis; D024042:Collagen Type I / Q000032:analysis; D015536:Down-Regulation / Q000235:genetics*; D005353:Fibronectins / Q000032:analysis; D020868:Gene Silencing; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009061:Mouth Mucosa / Q000293:injuries; D010159:Palate / Q000293:injuries*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics; D062326:Re-Epithelialization / Q000235:genetics; D051900:Smad3 Protein / Q000032:analysis* / Q000235:genetics; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D014945:Wound Healing / Q000235:genetics
chemical_list: D000199:Actins; C491768:Ccl2 protein, mouse; C496534:Ccl3 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D024042:Collagen Type I; D005353:Fibronectins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse
keywords: RNA interference; TGF-beta1; gene delivery systems; mouse; palatal wound-healing; targeted gene repair