title: The Role of EGFR/ERK/ELK-1 MAP Kinase Pathway in the Underlying Damage to Diabetic Rat Skin.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatological, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
authors.forename: Xinhong
authors.initials: X
authors.lastname: Ge
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Shi
authors.forename: Nan
authors.initials: N
authors.lastname: Yu
authors.forename: Yaning
authors.initials: Y
authors.lastname: Jiao
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Zhang
keywords: Activating transcription factors; diabetes; epidermal growth factor receptors; extracellular signal-regulated mitogen-activated protein kinases; skin