Canhamero Tatiane, Garcia Ludmila Valino, De Franco Marcelo
Laboratory of Immunogenetics, Butantan Institute , Secretary of Health, Government of the State of São Paulo, São Paulo, Brazil .
Adv Wound Care (New Rochelle). 2014 Sep 1;3(9):582-591. doi: 10.1089/wound.2013.0494.
Molecular biology techniques are being used to aid in determining the mechanisms responsible for tissue repair without scar formation. Wound healing is genetically determined, but there have been few studies that examine the genes responsible for tissue regeneration in mammals. Research using genetic mapping is extremely important for understanding the molecular mechanisms involved in the different phases of tissue regeneration. This process is complex, but an early inflammatory phase appears to influence lesion closure, and the present study demonstrates that acute inflammation loci influence tissue regeneration in mice in a positive manner. Mapping studies of quantitative trait loci (QTL) have been undertaken in recent years to examine candidate genes that participate in the regeneration phenotype. Our laboratory has identified inflammation modifier QTL for wound healing. Mouse lines selected for the maximum (AIRmax) or minimum (AIRmin) acute inflammatory reactivity (AIR) have been used to study not only the tissue repair but also the impact of the genetic control of inflammation on susceptibility to autoimmune, neoplasic, and infectious diseases. Murphy Roths Large and AIRmax mice are exclusive in their complete epimorphic regeneration, although middle-aged inbred mice may also be capable of healing. Inflammatory reactions have traditionally been described in the literature as negative factors in the process of skin injury closure. Inflammation is exacerbated due to the early release of mediators or the intense release of factors that cause cell proliferation after injury. The initial release of these factors as well as the clean-up of the lesion microenvironment are both crucial for following events. In addition, the activation and repression of some genes related to the regeneration phenotype may modulate lesion closure, demonstrating the significance of genetic studies to better understand the mechanisms involved in the initiation of wound repair processes. The pleiotropic effects of the QTL are important in the identification of the genes responsible for tissue repair processes, especially when combined with global gene expression research. Microarray analysis complements the biological information obtained in QTL mapping, making this tool essential for gene identification. This approach will allow the investigation of future targets for therapeutic wound healing treatments.
分子生物学技术正被用于协助确定无瘢痕组织修复的机制。伤口愈合由基因决定，但很少有研究探讨哺乳动物组织再生相关的基因。利用基因图谱进行的研究对于理解组织再生不同阶段所涉及的分子机制极为重要。这个过程很复杂，但早期炎症阶段似乎会影响伤口闭合，本研究表明急性炎症基因座对小鼠组织再生有积极影响。近年来已开展数量性状基因座（QTL）定位研究，以检测参与再生表型的候选基因。我们实验室已鉴定出伤口愈合的炎症调节QTL。选择具有最大（AIRmax）或最小（AIRmin）急性炎症反应性（AIR）的小鼠品系，不仅用于研究组织修复，还用于研究炎症的基因控制对自身免疫性、肿瘤性和感染性疾病易感性的影响。尽管中年近交系小鼠也可能具备愈合能力，但墨菲罗斯大（Murphy Roths Large）小鼠和AIRmax小鼠在完全再生方面独具特色。传统文献中将炎症反应描述为皮肤损伤闭合过程中的负面因素。由于损伤后介质的早期释放或导致细胞增殖的因子的强烈释放，炎症会加剧。这些因子的初始释放以及损伤微环境的清理对于后续事件都至关重要。此外，一些与再生表型相关基因的激活和抑制可能会调节伤口闭合，这表明基因研究对于更好地理解伤口修复过程起始所涉及的机制具有重要意义。QTL的多效性在确定负责组织修复过程的基因时很重要，尤其是与全基因组表达研究相结合时。微阵列分析补充了QTL定位中获得的生物学信息，使该工具成为基因鉴定的关键。这种方法将有助于研究未来治疗伤口愈合的靶点。
