Adenovirus-Mediated LAMA3 Transduction Enhances Hemidesmosome Formation and Periodontal Reattachment during Wound Healing
Adenovirus-Mediated LAMA3 Transduction Enhances Hemidesmosome Formation and Periodontal Reattachment during Wound Healing
复制标题
腺病毒介导的 LAMA3 转导增强伤口愈合过程中半桥粒的形成和牙周再附着
DOI：
10.1016/j.omtm.2020.06.001
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发表时间：
2020-09-11
影响因子：
4.7
通讯作者：
Yang, Guoli
中科院分区：
文献类型：
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作者：
Li, Yongzheng;Zhang, Jing;Yang, Guoli
一个强大的牙上皮连接防止外部致病因素进入结缔组织，可能是至关重要的牙周手术后牙周再附着。连接上皮（JE）通过半桥粒（HD）和内部基底层附着于牙齿表面，其中主要成分是层粘连蛋白-332。JE的破坏导致牙周附着的丧失。传统的治疗方法在消除牙龈局部炎症方面是有效的;然而，很少有直接促进牙周再附着和HD形成的。在这里，我们设计了一种基因治疗策略，使用腺病毒介导的人层粘连蛋白-332 α 3链（LAMA 3）基因（Ad-LAMA 3）转导到人永生化表皮细胞系（HaCaT），以研究在体外形成的HD。Ad-LAMA 3能促进HaCaT细胞早期粘附和快速迁移，并显著增加LAMA 3和XVII型胶原（BP 180）的表达。此外，HaCaT细胞可以促进LAMA 3过表达后成熟HDs的形成。体内实验表明，腺病毒介导的JE能增强LAMA 3和BP 180的表达，促进牙体与牙龈上皮的“生物封闭”。这些结果表明，腺病毒介导的LAMA 3转导是一种新的治疗策略，可促进伤口愈合过程中JE在牙齿周围的稳定性和整合。
A robust dento-epithelial junction prevents external pathogenic factors from entering connective tissue and could be crucial for periodontal reattachment after periodontal surgery. The junctional epithelium (JE) is attached to the tooth surface through the hemidesmosome (HD) and internal basal lamina, where the primary component is laminin-332. Destruction of the JE leads to the loss of periodontal attachment. Traditional treatments are effective in eliminating local inflammation of the gingiva; however, few directly promote periodontal reattachment and HD formation. Here, we designed a gene-therapy strategy using the adenovirus-mediated human laminin-332 alpha 3 chain (LAMA3) gene (Ad-LAMA3) transduced into a human-immortalized epidermal cell line (HaCaT) to study the formation of HD in vitro. Ad-LAMA3 promoted early adhesion and fast migration of HaCaT cells and increased expression of LAMA3 and type XVII collagen (BP180) significantly. Furthermore, HaCaT cells could facilitate formation of mature HDs after LAMA3 overexpression. In vivo experiments demonstrated that the JE transduced with Ad-LAMA3 could increase expression of LAMA3 and BP180 and "biological sealing" between the tooth and gingival epithelium. These results suggested that adenovirus-mediated LAMA3 transduction is a novel therapeutic strategy that promotes the stability and integration of the JE around the tooth during wound healing.