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Int. J. Mol. Sci. 2016, 17(11), 1961; doi:10.3390/ijms17111961

HMGB1 Promotes Intraoral Palatal Wound Healing through RAGE-Dependent Mechanisms

1
Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand
2
Department of Emergency and Critical Care, Hokkaido University, Kita-ku, Sapporo 0608648, Japan
3
Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 8908544, Japan
4
Division of Brain Science, Department of Physiology, Kurume University School of Medicine, Asahi-machi, Kurume 8300011, Japan
5
Department of Anesthesiology and Intensive Care, Hokkaido Medical for Child Health and Rehabilitation, Sapporo 0060041, Japan
6
Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
*
Author to whom correspondence should be addressed.
Academic Editor: Allison Cowin
Received: 15 September 2016 / Revised: 5 November 2016 / Accepted: 15 November 2016 / Published: 23 November 2016
(This article belongs to the Special Issue Wound Repair and Regeneration)
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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 between Hmgb1+/− and WT mice on Day 3 after wounding. Mallory Azan staining showed densely packed of collagen fibers in WT mice, whereas in Hmgb1+/− 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 of Hmgb1+/− 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. View Full-Text
Keywords: HMGB1; NF-κB; wound healing; palatal mucosa HMGB1; NF-κB; wound healing; palatal mucosa
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Tancharoen, S.; Gando, S.; Binita, S.; Nagasato, T.; Kikuchi, K.; Nawa, Y.; Dararat, P.; Yamamoto, M.; Narkpinit, S.; Maruyama, I. HMGB1 Promotes Intraoral Palatal Wound Healing through RAGE-Dependent Mechanisms. Int. J. Mol. Sci. 2016, 17, 1961.

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