表皮生长因子受体/细胞外信号调节激酶/ELK-1丝裂原活化蛋白激酶信号通路在糖尿病大鼠皮肤潜在损伤中的作用
The Role of EGFR/ERK/ELK-1 MAP Kinase Pathway in the Underlying Damage to Diabetic Rat Skin.
作者信息
Ge Xinhong, Shi Zhiyun, Yu Nan, Jiao Yaning, Jin Li, Zhang Jianzhong
机构信息
Department of Dermatological, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
出版信息
Indian J Dermatol. 2013 Mar;58(2):101-6. doi: 10.4103/0019-5154.108035.
BACKGROUND
Diabetes mellitus (DM) is a highly prevalent disease. Atrophy and spontaneous ulcers are the most common cutaneous manifestation of diabetic dermopathy (DD). Before spontaneous ulcers, we believe there is an underlying damage stage although the mechanism is unknown.
AIMS
To explore the expression of extracellular signal-regulated kinase1/2 (ERK1/2), its correlated upstream protein epidermal growth factor receptor (EGFR) and its downstream transcription factor E twenty-six (ETS)-like 1(ELK-1)in the damage of the diabetic rat skin, and to explore the role of ERK1/2 on the recessive damage to diabetic rat skin.
MATERIALS AND METHODS
Eighty Sprague-Dawley (SD) rats weighing 260-300 g were randomly divided into control and streptozotocin (STZ)-induced diabetes groups. After 0.5, 2, 4, and 8 weeks, the shaved skin specimens from the back of rats in both groups were collected to observe the histological characteristics of the skin, to measure the thickness of the epidermis and the dermis, and to observe the ultrastructure. Immunohistochemistry (IHC) and Western blot techniques were used to detect the expression and activation of ERK1/2, EGFR, ELK-1 in the skin of the rats.
RESULTS
There are ultrastructural changes in the DM skin. With the continuance of the diabetes course, the thicknesses of the epidermis and dermis decreased, and the expression of phospho-ERK1/2 (P-ERK1/2), EGFR, and ELK-1 was decreased gradually in the back skin of the diabetes rats. It was significantly lower in 4 and 8 week DM than that of the normal control (P < 0.05). The expression of P-EGFR and P-ERK1/2 in the back skin of the diabetes rats was positively correlated (r = 0.572 P < 0.05), and the positive correlation was also obtained between P-ERK1/2 and P-ELK-1 (r = 0.715, P < 0.05).
CONCLUSION
THE PHENOMENON OF RECESSIVE DAMAGE EXISTS IN THE SKIN OF DIABETES RATS, WHICH PROBABLY MAY RELATE TO THE WEAKNESS OF THE SIGNAL TRANSDUCTION: P-EGFR → ERK1/2 → ELK-1.
背景
糖尿病（DM）是一种高度流行的疾病。萎缩和自发性溃疡是糖尿病性皮肤病（DD）最常见的皮肤表现。在自发性溃疡出现之前，我们认为存在一个潜在的损伤阶段，尽管其机制尚不清楚。
目的
探讨细胞外信号调节激酶1/2（ERK1/2）、其相关上游蛋白表皮生长因子受体（EGFR）及其下游转录因子E26（ETS）样因子1（ELK-1）在糖尿病大鼠皮肤损伤中的表达，并探讨ERK1/2在糖尿病大鼠皮肤隐性损伤中的作用。
材料与方法
将80只体重260 - 300 g的Sprague-Dawley（SD）大鼠随机分为对照组和链脲佐菌素（STZ）诱导的糖尿病组。0.5、2、4和8周后，收集两组大鼠背部剃毛后的皮肤标本，观察皮肤的组织学特征，测量表皮和真皮的厚度，并观察超微结构。采用免疫组织化学（IHC）和蛋白质印迹技术检测大鼠皮肤中ERK1/2、EGFR、ELK-1的表达及活化情况。
结果
糖尿病大鼠皮肤存在超微结构改变。随着糖尿病病程延长，糖尿病大鼠背部皮肤表皮和真皮厚度降低，磷酸化ERK1/2（P-ERK1/2）、EGFR和ELK-1的表达逐渐降低。糖尿病4周和8周组明显低于正常对照组（P < 0.05）。糖尿病大鼠背部皮肤中P-EGFR与P-ERK1/2的表达呈正相关（r = 0.572，P < 0.05），P-ERK1/2与P-ELK-1之间也呈正相关（r = 0.715，P < 0.05）。
结论
糖尿病大鼠皮肤存在隐性损伤现象，这可能与信号转导P-EGFR→ERK1/2→ELK-1减弱有关。
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