Health Management Center, First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing 400038, China.
Department of Endocrinology, First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing 400038, China.
Mediators Inflamm. 2019 Mar 17;2019:6705424. doi: 10.1155/2019/6705424. eCollection 2019.
Chronic diabetic foot ulcer (DFU) is one of the most intractable complications of diabetes mellitus (DM). Its pathogenesis is complex, and uncontrolled chronic inflammation is an important factor. Endothelial overexpressed lipopolysaccharide-associated factor 1 (EOLA1) discovered in our laboratory is an intracellular protein with the function of inflammatory regulation. This study was aimed at observing the expression of EOLA1 in DFU skin tissues and its relationship with inflammation and at exploring the possible role of EOLA1 in DFU and its mechanism.
The patients with DFU were divided into 2 groups based on the formation time of ulcer: the acute wound (AW) group with the course of disease ≤ 4 weeks and the chronic wound (CW) group with the course of disease > 4 weeks. The relevant clinical data of patients were collected, and the skin tissues around the ulcer were used for immunofluorescence detection and immunohistochemical staining to observe inflammation. The expression levels of EOLA1, metallothionein 2A (MT2A), nuclear factor-B (NF-B), and interleukin-6 (IL-6) were detected by western blot.
A total of 79 patients were enrolled in the study. The results of immunofluorescence and immunohistochemistry showed that EOLA1 was expressed in the epithelial tissues of DFU. However, the expression of EOLA1 in the CW group was significantly lower than that in the AW group ( < 0.05), and the expression of NF-B and IL-6 was obviously increased ( < 0.05).
The refractory wounds in patients with DFU may be closely related to the uncontrolled activation of inflammatory pathways in cells caused by the reduced expression of negative regulators of inflammation (e.g., EOLA1), and such decreased expression may be also strongly linked to the persistent state of inflammation.
慢性糖尿病足溃疡(DFU)是糖尿病(DM)最棘手的并发症之一。其发病机制复杂,慢性炎症失控是一个重要因素。本实验室发现的内皮细胞过度表达的脂多糖相关因子 1(EOLA1)是一种具有炎症调节功能的细胞内蛋白。本研究旨在观察 EOLA1 在 DFU 皮肤组织中的表达及其与炎症的关系,并探讨 EOLA1 在 DFU 中的可能作用及其机制。
根据溃疡形成时间将 DFU 患者分为 2 组:病程≤4 周的急性创面(AW)组和病程>4 周的慢性创面(CW)组。收集患者的相关临床资料,取溃疡周围皮肤组织进行免疫荧光检测和免疫组织化学染色,观察炎症情况。采用 Western blot 检测 EOLA1、金属硫蛋白 2A(MT2A)、核因子-B(NF-B)和白细胞介素-6(IL-6)的表达水平。
共纳入 79 例患者。免疫荧光和免疫组化结果显示,EOLA1 在 DFU 的上皮组织中表达。然而,CW 组 EOLA1 的表达明显低于 AW 组(<0.05),NF-B 和 IL-6 的表达明显增加(<0.05)。
DFU 患者的难治性创面可能与炎症负调控因子(如 EOLA1)表达减少导致细胞内炎症途径失控有关,这种表达减少可能与炎症的持续状态密切相关。