Soley Bruna da Silva, Morais Rafael Leite Tavares de, Pesquero João Bosco, Bader Michael, Otuki Michel Fleith, Cabrini Daniela Almeida
Department of Pharmacology, Universidade Federal do Paraná, Curitiba, PR, Brazil.
Department of Biophysics, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
J Dermatol Sci. 2016 May;82(2):95-105. doi: 10.1016/j.jdermsci.2016.01.007. Epub 2016 Jan 15.
Wound healing is a complex and dynamic process that includes 3 different phases: inflammation, proliferation, and remodeling. Kinins are vasoactive peptides released after tissue injury, and are directly involved in the development and maintenance of inflammatory processes, and their actions are mediated by the activation of receptors called B1 and B2.
We aimed to evaluate the involvement of kinin receptors in the skin healing process.
Knockout mice for kinin receptors (KOB1, KOB2 and KOB1B2) and wild type controls (WT) were subjected to a skin excision model, and tissue repair process was evaluated during different phases of wound healing.
In knockout animals for kinin receptors differences were observed in the resolution period of injury exceeding 17 days for the total closure of wounds. The absence of kinin receptors promotes a significant reduction in infiltration of polymorphonuclear cells on day 2 of the inflammatory phase. Already at the late stage of this phase (3 days) there was a negative influence on the infiltration of polymorphonuclear and mononuclear cells at the site of injury in comparison to WT. Collagen was significantly diminished in tissue of KOB1, KOB2 and KOB1B2 from day two to the end of the healing process. Moreover, wound tissue from KOB2 and KOB1B2, but not KOB1, presented impaired parameters of re-epitheliazation, reduced proliferation of cells (PCNA immunostaining), and a lower number of myofibroblasts (α-SMA immunostaining).
These data reveal the involvement of kinin receptors in processes of skin repair. Both kinin receptors participate especially during the inflammatory phase, while B2 receptors seem to be more relevant in the quality of the wound scar. Thus, a better understanding of the contribution of kinins to skin wound healing may reveal novel options for therapy.
伤口愈合是一个复杂且动态的过程，包括三个不同阶段：炎症期、增殖期和重塑期。激肽是组织损伤后释放的血管活性肽，直接参与炎症过程的发生和维持，其作用通过名为B1和B2的受体激活介导。
我们旨在评估激肽受体在皮肤愈合过程中的作用。
对激肽受体基因敲除小鼠（KOB1、KOB2和KOB1B2）和野生型对照（WT）进行皮肤切除模型实验，并在伤口愈合的不同阶段评估组织修复过程。
在激肽受体基因敲除动物中，观察到损伤愈合期存在差异，伤口完全闭合超过17天。激肽受体缺失导致炎症期第2天多形核细胞浸润显著减少。与野生型相比，在该阶段后期（3天），损伤部位的多形核细胞和单核细胞浸润受到负面影响。从愈合过程的第2天到结束，KOB1、KOB2和KOB1B2组织中的胶原蛋白显著减少。此外，KOB2和KOB1B2的伤口组织（而非KOB1）出现上皮再形成参数受损、细胞增殖减少（PCNA免疫染色）以及肌成纤维细胞数量减少（α-SMA免疫染色）。
这些数据揭示了激肽受体参与皮肤修复过程。两种激肽受体尤其在炎症期发挥作用，而B2受体似乎在伤口瘢痕质量方面更为重要。因此，更好地理解激肽对皮肤伤口愈合的作用可能会揭示新的治疗选择。
