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首页> 外文期刊>International Journal of Nanomedicine >Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO
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Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO

机译：通过局部皮下注射纳米级rhEPO结合EPO受体和β共同受体的表达，深层二级烫伤具有圆锥形和毛囊结构的皮肤再生

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Background: Acceleration of skin regeneration is still an unsolved problem in the clinical treatment of patients suffering from deep burns and scalds. Although erythropoietin (EPO) has a protective role in a wide range of organs and cells during ischemia and after trauma, it has been recently discovered that EPO is not tissue-protective in the common β subunit receptor (βCR) knockout mouse. The protective capacity of EPO in tissue is mediated via a heteroreceptor complex comprising both the erythropoietin receptor (EPOR) and βCR. However, proof of coexpression of these heterogenic receptors in regenerating skin after burns is still lacking.Methods: To understand the role of nanosized recombinant human erythropoietin (rhEPO) in wound healing, we investigated the effects of subcutaneous injections of EPO on skin regeneration after deep second-degree scalding injuries. Our aim was to determine if joint expression of EPOR and βCR is a prerequisite for the tissue-protective effect of rhEPO. The efficiency in wound regeneration in a skin scalding injury mouse model was examined. A deep second-degree dermal scald injury was produced on the backs of 20 female Balb/c mice which were subsequently randomized to four experimental groups, two of which received daily subcutaneous injections of rhEPO. At days 7 and 14, the mice were sacrificed and the effects of rhEPO were analyzed with respect to grade of re-epithelialization (wound closure) and stage of epidermal maturation. This was investigated using different histological parameters of epithelial covering, such as depth of the epidermal layer, epidermal stratification, and presence of conical and hair follicle structures.Results: Expression of EPOR, βCR, and growth hormone receptor at the mRNA and protein levels was demonstrated with reverse transcriptase polymerase chain reaction and Western blot analysis. After rhEPO treatment, the rate of re-epithelialization of the scalding injury was increased and the time to final wound closure was reduced. In addition, the quality of regenerated skin was improved. In this investigation, for the first time, we demonstrated coexpression of EPOR and βCR at the RNA and protein levels in vivo using a deep second-degree scalding injury mouse model. These results highlight the potential role of rhEPO in the improved treatment of burns patients, which might be crucial for the development of innovative new therapy regimes.Conclusion: Local injection of nanosized rhEPO directly to the injury site rather than systemic administration for deep second-degree scalding injuries achieved complete skin regeneration with conical and hair follicle structure via combined expression of EPOR and βCR.
机译：背景：在严重烧伤和烫伤患者的临床治疗中，加速皮肤再生仍然是尚未解决的问题。尽管促红细胞生成素（EPO）在局部缺血期间和创伤后对多种器官和细胞具有保护作用，但最近发现EPO在常见的β亚基受体（βCR）敲除小鼠中没有组织保护作用。 EPO在组织中的保护能力是通过同时包含促红细胞生成素受体（EPOR）和βCR的异受体复合物介导的。然而，仍然缺乏在烧伤后再生皮肤中这些异源受体共表达的方法。方法：为了了解纳米级重组人促红细胞生成素（rhEPO）在伤口愈合中的作用，我们研究了深层后皮下注射EPO对皮肤再生的影响。二级烫伤。我们的目的是确定EPOR和βCR的联合表达是否是rhEPO组织保护作用的先决条件。检查了皮肤烫伤小鼠模型中伤口再生的效率。在20只雌性Balb / c小鼠的背部产生了严重的二级皮肤烫伤，随后将其随机分为四个实验组，其中两个每天接受皮下注射rhEPO。在第7天和第14天，处死小鼠，并分析rhEPO对再上皮形成的程度（伤口闭合）和表皮成熟阶段的作用。使用不同的上皮组织学参数进行了研究，例如表皮层的深度，表皮分层以及圆锥形和毛囊结构的存在。用逆转录酶聚合酶链反应和蛋白质印迹分析证实。 rhEPO治疗后，烫伤损伤的再上皮率增加，最终伤口闭合的时间减少。另外，改善了再生皮肤的质量。在这项研究中，我们首次使用深度二级烫伤小鼠模型在体内RNA和蛋白质水平上证明了EPOR和βCR的共表达。这些结果突显了rhEPO在改善烧伤患者治疗中的潜在作用，这可能对创新性新疗法的发展至关重要。烫伤可通过EPOR和βCR的联合表达实现圆锥形和毛囊结构的完全皮肤再生。

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