HMGB1 Promotes Intraoral Palatal Wound Healing through RAGE-Dependent Mechanisms.

HMGB1 Promotes Intraoral Palatal Wound Healing through RAGE-Dependent Mechanisms.
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DOI:
10.3390/ijms17111961
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发表时间:
2016-11-23
影响因子:
5.6
通讯作者:
Maruyama I
Maruyama I
中科院分区:
生物学2区
文献类型:
--
作者:
Tancharoen S;Gando S;Binita S;Nagasato T;Kikuchi K;Nawa Y;Dararat P;Yamamoto M;Narkpinit S;Maruyama I

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高迁移率族蛋白1(HMGB 1)与组织损伤后的组织组织化过程密切相关。在这里,我们表明,HMGB 1控制上皮和结缔组织再生在体内和体外腭伤口愈合。使杂合HMGB 1(Hmgb 1 +/−)小鼠和野生型(WT)小鼠经受腭损伤。上颌组织用马洛里Azan染色或用抗HMGB 1、抗增殖细胞核抗原(PCNA)、抗核因子-κB(NF-κB)p50和抗血管内皮生长因子(VEGF)抗体免疫染色。腭牙龈组织块与重组HMGB 1(rHMGB 1)共同培养,并与靶向晚期糖基化终产物受体(RAGEs)的siRNA共同处理,以进行细胞迁移和PCNA表达分析。创伤后第3天,Hmgb 1 +/−和WT小鼠的创伤面积测量结果存在差异。马洛里Azan染色显示WT小鼠中胶原纤维密集,而Hmgb 1 +/−小鼠中存在编织样低密度胶原束。在术后3天和7天,WT小鼠的PCNA、NF-κB p50和VEGF阳性角质形成细胞大于Hmgb 1 +/−小鼠。在牙龈细胞培养物中,敲除rHMGB 1可阻止rHMGB 1诱导的细胞迁移和PCNA表达。这些数据表明,HMGB 1/HMGB 2轴在腭创伤愈合中起着至关重要的作用。
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.
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