title: HMGB1 Promotes Intraoral Palatal Wound Healing through RAGE-Dependent Mechanisms.
abstract: High mobility group box 1 (HMGB1) is tightly connected to the process of tissue organization upon tissue injury. Here we show that HMGB1 controls epithelium and connective tissue regeneration both in vivo and in vitro during palatal wound healing. Heterozygous HMGB1 (Hmgb1+/-) mice and Wild-type (WT) mice were subjected to palatal injury. Maxillary tissues were stained with Mallory Azan or immunostained with anti-HMGB1, anti-proliferating cell nuclear antigen (PCNA), anti-nuclear factor-κB (NF-κB) p50 and anti-vascular endothelial growth factor (VEGF) antibodies. Palatal gingival explants were cultured with recombinant HMGB1 (rHMGB1) co-treated with siRNA targeting receptor for advanced glycation end products (RAGEs) for cell migration and PCNA expression analysis. Measurement of the wound area showed differences betweenHmgb1+/-and WT mice on Day 3 after wounding. Mallory Azan staining showed densely packed of collagen fibers in WT mice, whereas inHmgb1+/-mice weave-like pattern of low density collagen bundles were present. At three and seven days post-surgery, PCNA, NF-κB p50 and VEGF positive keratinocytes of WT mice were greater than that ofHmgb1+/-mice. Knockdown of RAGE prevents the effect of rHMGB1-induced cell migration and PCNA expression in gingival cell cultures. The data suggest that HMGB1/RAGE axis has crucial roles in palatal wound healing.
authors.affiliation: Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand. salunya.tan@mahidol.ac.th.
authors.forename: Salunya
authors.initials: S
authors.lastname: Tancharoen
authors.affiliation: Department of Emergency and Critical Care, Hokkaido University, Kita-ku, Sapporo 0608648, Japan. gando@med.hokudai.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Gando
authors.affiliation: Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 8908544, Japan. binita@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Shrestha
authors.initials: S
authors.lastname: Binita
authors.affiliation: Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 8908544, Japan. n-tomoka@m.kufm.kagoshima-u.ac.jp.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Nagasato
authors.affiliation: Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand. kikuchi_kiyoshi@kurume-u.ac.jp.|Division of Brain Science, Department of Physiology, Kurume University School of Medicine, Asahi-machi, Kurume 8300011, Japan. kikuchi_kiyoshi@kurume-u.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kikuchi
authors.affiliation: Department of Anesthesiology and Intensive Care, Hokkaido Medical for Child Health and Rehabilitation, Sapporo 0060041, Japan. nawa@sapmed.ac.jp.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nawa
authors.affiliation: Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand. pornpen.dar@mahidol.ac.th.
authors.forename: Pornpen
authors.initials: P
authors.lastname: Dararat
authors.affiliation: Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 8908544, Japan. m-yamamo@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Mika
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand. somphong.nar@mahidol.ac.th.
authors.forename: Somphong
authors.initials: S
authors.lastname: Narkpinit
authors.affiliation: Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 8908544, Japan. rinken@m3.kufm.kagoshima-u.ac.jp.
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D005786:Gene Expression Regulation; D005881:Gingiva / Q000293:injuries / Q000378:metabolism; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008437:Maxilla / Q000293:injuries / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009061:Mouth Mucosa / Q000293:injuries / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D021362:Palate, Hard / Q000293:injuries / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics*
chemical_list: C000593873:Ager protein, mouse; D000911:Antibodies, Monoclonal; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D052002:NF-kappa B p50 Subunit; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse
keywords: HMGB1; NF-κB; palatal mucosa; wound healing