The Role of EGFR/ERK/ELK-1 MAP Kinase Pathway in the Underlying Damage to Diabetic Rat Skin

EGFR/ERK/ELK-1 MAP激酶通路在糖尿病大鼠皮肤潜在损伤中的作用

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作者:Xinhong Ge, Zhiyun Shi, Nan Yu, Yaning Jiao, Li Jin, Jianzhong Zhang

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

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

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.

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).

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