Impaired permeability and antimicrobial barriers in type 2 diabetes skin are linked to increased serum levels of advanced glycation end-product
Impaired permeability and antimicrobial barriers in type 2 diabetes skin are linked to increased serum levels of advanced glycation end-product
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DOI：
10.1111/exd.13466
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发表时间：
2018-08-01
影响因子：
3.6
通讯作者：
Choi, Eung Ho
中科院分区：
文献类型：
--
作者：
Kim, Jae-Hong;Yoon, Na Young;Choi, Eung Ho
2型糖尿病（type 2 diabetes mellitus，DM）的发病率呈快速上升趋势，已成为严重的社会医学问题。许多皮肤问题，如干燥、瘙痒、皮肤感染和伤口愈合延迟，可能与皮肤屏障功能的慢性损害有关，降低了DM患者的生活质量。然而，DM皮肤的渗透性和抗菌屏障的状态仍然未知。本研究采用经典的2型糖尿病动物模型，探讨2型糖尿病患者皮肤屏障功能损害及其病理机制。比较了2型糖尿病患者和年龄、性别匹配的非糖尿病对照组的皮肤屏障功能研究和角质层（SC）脂质分析。此外，使用2型DM动物模型，db/db和ob/ob小鼠进行皮肤屏障，表皮脂质分析，电子显微镜和生物分子研究的功能研究。2型DM患者表现为表皮屏障损伤，包括SC水合作用，这受到血糖控制（HbA 1c水平）的影响。在SC的脂质分析中，与对照组相比，2型DM患者的神经酰胺、脂肪酸和胆固醇显著降低。2型DM小鼠模型表现为重度高血糖、皮肤屏障稳态受损、表皮增殖和表皮脂质合成减少、板层体（LB）和表皮抗菌肽（AMP）减少、表皮中晚期糖基化终产物（AGE）受体增加和血清AGE增加。在2型DM中观察到皮肤屏障受损，这部分是由于表皮增殖减少。2型糖尿病小鼠的血清AGE及其表皮受体增加，这些小鼠表现出皮肤屏障参数受损，例如表皮脂质合成、LB产生、表皮AMP和SC脂质。
The incidence of type 2 diabetes mellitus (DM) has been increasing rapidly, and the disease has become a serious sociomedical problem. Many skin problems, such as xerosis, pruritus, skin infections and delayed wound healing, that might be related to chronic impairment of skin barrier function decrease the quality of life in patients with DM. However, the status of the permeability and antimicrobial barrier of the skin in DM remains unknown. This study aimed to elucidate skin barrier impairment in patients with type 2 DM and its pathomechanisms using classic animal models of type 2 DM. Functional studies of the skin barrier and an analysis of stratum corneum (SC) lipids were compared between patients with type 2 DM and age- and sex-matched non-diabetes controls. Also, functional studies on the skin barrier, epidermal lipid analyses, and electron microscopy and biomolecular studies were performed using type 2 DM animal models, db/db and ob/ob mice. Patients with type 2 DM presented with epidermal barrier impairments, including SC hydration, which was influenced by blood glucose control (HbA1c level). In the lipid analysis of SC, ceramides, fatty acids and cholesterol were significantly decreased in patients with type 2 DM compared with controls. Type 2 DM murine models presented with severe hyperglycaemia, impairment of skin barrier homeostasis, decreases in epidermal proliferation and epidermal lipid synthesis, decreases in lamellar body (LB) and epidermal antimicrobial peptides (AMPs), an increase in receptors for advanced glycation end-product (AGE) in the epidermis and an increase in serum AGE. Impairment of the skin barrier was observed in type 2 DM, which results in part from a decrease in epidermal proliferation. Serum AGE and its epidermal receptors were increased in type 2 diabetic mice which display impaired skin barrier parameters such as epidermal lipid synthesis, LB production, epidermal AMP and SC lipids.