Role Of P-ERK,IGF-1R,PTEN And PCNA In Pathologic Scar Formation

Pathologic scar include hypertrophic scar and keloid scar.In histology, Pathologic scar are characterized by excessive accumulation of fibroblasts and extracellular matrix, expecially collagen. the explanation of overmuch proliferation and lack of apoptosis of fibroblasts become the hotspot in the study of pathogenesis of pathologic scar now. With the further study, many scholar find fibroblastic irritative cytokine transfer proliferous signaling through the routeway of PTK→Ras→Raf-1→ERK, ERK become enabled and fibroblasts is proliferous. p-ERK can accelerate cell proliferation and differentiation. IGF-1R represses apoptosis and promotes karyokinesis of cell. PTEN regulates cell normal development, avoids its overmuch proliferation through antagonizing PTK. PCNA is tightly associated with somatic cell proliferation. The expression of p-ERK, IGF-1R and PTEN protein in pathologic scar and the correlation with the expression of PCNA are not clear, the correlation between the expression of IGF-1R, PTEN and that of p-ERK are also not clear. So,we detect the expressions and significance of p-ERK, IGF-IR PTEN and PCNA in fibroblasts derived from pathologic scar that Total 40 samples were detected by using immunnohistochemistry method to investigate the relationship between expressions of these proteins and the formation of pathologic scar. Materials and methods:The tissues of pathologic scar were obtained from 40 patients who were underwent surgery; Scar tissues were collected from face, neck, chest, shoulder abdomen and limbs. Pathologic scar were divided into two groups according to their clinical features: 1.Hypertrophic Scar(HS): Duration: 6-24 months, hypertrophic scar remain with theboundaries of the original wound. 2.Keloid: Duration: 6-24 months, keloid extend beyond the original area of skin injury. Twenty cases of normal skin collected from patients with pathologic scar and ten cases of normotrophic scar which are charactered by no redness, pruritus, pain, and flattened with surrounded skin were used as control. Normotrophic scars were collected from face, neck and limbs. Immunohistochernical SP method were used to detect expressions of ERK, IGF-1R PTEN and PCNA in pathologic scar and the two control groups, and correlations among expressions of these proteins were systematically studied. The data was analysed through package of software spssl 3.0, and significance level is a =0.05, and a =0.0167 after x 2 division. Results:1. The positive expression of p-ERK was mainly localized in the cytoplasm of fibroblasts, the positive rates in pathologic scars were 80.00% (32/40), 30.00% (6/20X 15.00%(3/20) respectively in normotrophic scars and normal skins. The expression of p-ERK were significant difference between pathologic scars group and the two control groups(P<0.0167), the expression of p-ERK were not significant difference between the two control groups(P>0.0167)2. In pathologic scars group, the positive expression was mainly localized in the cytoplasm of epidermal cells, great mass of fibroblasts and part of blood vessal endodermiscell. The positive rates of IGF-1R were 75.00% (30/40)n 25.00% (5/20)> 15.00% (3/20) respectively in pathologic scars, normotrophic scars and normal skins.There was significant difference between pathologic scars group and two control groups in the expression of IGF-lR(P<0.0167), There was not significant difference in the expression of IGF-1R between the two control gfovtps(P>0.0l67).3. In normal skin group, the positive expression was mainly localized in the cytoplasm of epidermal cells, great mass of fibroblasts and part of blood vessal endodermiscell. The positive rates of PTEN were 17.50% (7/40), 70.00% (14/20), 90.00% (18/20) respectively in pathologic scars, normotrophic scars and normal skins. There was significant difference in the expression of PTEN between pathologic scars group and the two control groups.(P<0.0167), There was not significant difference in the expression of PTEN between the two control groups(P>0.0167).4. The expression of PCNA was localized in the nuclei. In pathologic scar, normtrophic scar and normal skin, PCNA proliferative index(PI) were 36.13 ± 17.4 K 9.75 ± 9.51 and 7.40+8.55. PCNA PI was higher in pathologic scar and there was significant difference between pathologic scar group and the two control groups (P<0.05).5. Correlativity analysis showed the expression of p-ERK and IGF-1R was positively correlated with PCNA(P<0.05), the expression of PTEN was negatively correlated with PCNA(p<0.05), the expression of IGF-1R was positively correlated with p-ERK (PO.05) and the expression of PTEN was negatively correlated with ERK(P<0.05) Conclusions:1. p-ERK is the convergent point of ERK signaling transduction pathway, its activation can accelerate cell proliferation and differentiation. In pathologic scar, overexpression of p-ERK suggests the formation of pathologic scar could be the result of highly proliferative activity of fibroblasts.2. The expression of IGF-1R was positive correlated with p-ERK suggests IGF-1R could improve the expression of p-ERK and play a coordinated role in pathologic scar formation.3. The expression of PTEN was negatively correlated with p-ERK suggests PTEN could reduce the expression of p-ERK and play a prohibitive role in pathologic scar formation.4. The positive expression of p-ERK, IGF-1R and the negatively expression of PTEN in pathologic scar suggest the formation of pathologic scar may be associated with the imbalance if regulation among extracellular regulated protein kinase signaling transmission pathway.