Department of Veterinary Medicine, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
Department of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
Oxid Med Cell Longev. 2020 Dec 7;2020:8862953. doi: 10.1155/2020/8862953. eCollection 2020.
Cytokines and growth factors are known to play an important role in the skin wound closure process; however, in knockout organisms, the levels of these molecules can undergo changes that result in the delay or acceleration of this process. Therefore, we systematically reviewed evidence from preclinical studies about the main immunoregulatory molecules involved in skin repair through the analysis of the main mechanisms involved in the depletion of immunoregulatory genes, and we carried out a critical analysis of the methodological quality of these studies. We searched biomedical databases, and only original studies were analyzed according to the PRISMA guidelines. The included studies were limited to those which used knockout animals and excision or incision wound models without intervention. A total of 27 studies were selected; data for animal models, gene depletion, wound characteristics, and immunoregulatory molecules were evaluated and compared whenever possible. Methodological quality assessments were examined using the ARRIVE and SYRCLE's bias of risk tool. In our review, the extracellular molecules act more negatively in the wound healing process when silenced and the metabolic pathway most affected involved in these processes was TGF-/Smad, and emphasis was given to the importance of the participation of macrophages in TGF- signaling. Besides that, proinflammatory molecules were more evaluated than anti-inflammatory ones, and the main molecules evaluated were, respectively, TGF-1, followed by VEGF, IL-6, TNF-, and IL-1. Overall, most gene depletions delayed wound healing, negatively influenced the concentrations of proinflammatory cytokines, and consequently promoted a decrease of inflammatory cell infiltration, angiogenesis, and collagen deposition, compromising the formation of granulation tissue. The studies presented heterogeneous data and exhibited methodological limitations; therefore, mechanistic and highly controlled studies are required to improve the quality of the evidence.
细胞因子和生长因子在皮肤伤口愈合过程中起着重要作用；然而，在基因敲除生物中，这些分子的水平可能会发生变化，导致该过程的延迟或加速。因此，我们系统地回顾了关于参与皮肤修复的主要免疫调节分子的临床前研究证据，通过分析参与免疫调节基因耗竭的主要机制，对这些研究的方法学质量进行了批判性分析。我们检索了生物医学数据库，仅根据 PRISMA 指南分析了原始研究。纳入的研究仅限于使用基因敲除动物和切除或切口伤口模型且无干预的研究。共选择了 27 项研究；尽可能评估和比较了动物模型、基因耗竭、伤口特征和免疫调节分子的数据。使用 ARRIVE 和 SYRCLE 的偏倚风险工具评估了方法学质量评估。在我们的综述中，当沉默时，细胞外分子在伤口愈合过程中表现出更负面的作用，受这些过程影响最大的代谢途径是 TGF-/Smad，并且强调了巨噬细胞参与 TGF-信号的重要性。除此之外，促炎分子比抗炎分子受到更多的评估，评估的主要分子分别是 TGF-1，其次是 VEGF、IL-6、TNF-和 IL-1。总体而言，大多数基因耗竭会延迟伤口愈合，对促炎细胞因子的浓度产生负面影响，从而减少炎症细胞浸润、血管生成和胶原蛋白沉积，损害肉芽组织的形成。这些研究的数据存在异质性，且存在方法学局限性；因此，需要进行机制和高度受控的研究以提高证据质量。
