The Expression Of Integrinβ₁, E2F1 In Hypertrophic Scars And Their Relationship To Microvessel Density

Background and objectivePathologic scars include hypertrophic scar (HS ) and keloid (K) , which are the appearance of excessive fibrosis in wound reparation. Their characteristic is the abnormal proliferation of fibroblast and the following secretion of generous extracelluar matrix (ECM) .The researches on the mechanism and curation of Pathologic scar have made big progress. And they show that the development, growth and turnover refer to synthesis and degradation of extracelluar matrix, cell factors, the regulation of cell cycle, and so on. As a adhesion molecule, Integrins can mediate adhesion between cells or between cells and extracelluarmatrix, which can mediate the transmission of physical and chemical information. By this Integrins eventually participate proliferation, differentiation, apoptosis and cell cycle. E2F is a nuclear factor (NF) which can promote the cell proliferation. CD105 is a blood vessel marker. The correlation between the expression of Integrinβ₁ and E2F1 is not clear. Another correlation between their expression and the vascularization in Pathologic scar are also not clear, either. This research is to study the expression of Integrinβ₁, E2F₁, and their relations with the microvessel density (MVD) marked by CD105, in order to approach Integrins' effection during the generation and development of Pathologic scar.Materials and methodsThe forty cases of Pathologic scars as the experimental group are obtained from patients from of 2004 to 2006. The twenty cases of normotrophic scars, which have no flare or itch, and are soft and flat. They were all obtained from cleft lip or external injury patients. The twenty cases of normal skin which were chosen as control groups came from normal skin of Pathological scars patients or full thick skin grafts. The S-P immunohistochemical technique was used to detect the expression of Integrinβ₁, E2F and MVD which was marked by CD105 (CD105-MVD) in the development of Pathologic scars.The statistics data were processed by SPSS 13.0, using ANOVA, T test and Dependability analysis. The test standard is 0.05 and the standard of x² division is 0.0167.Results1. Integrinβ₁ expressed mainly on the cell membrane or cytoplasm of fibroblasts and cell membrane of basal cells. There was a statistical significance between the Pathologic scars and normotrophic scars or normal skin (P<0.0167). There was no statistical significance between normotrophic scars scars and normal skin (P> 0.0167).2. E2F1 expressed mainly on the cell nucleus of fibroblasts and partly on the cell nucleus of endothelial cell. There was a statistical significance between the Pathologic scars and normotrophic scars or normal skin (P< 0.0167). There was no statistical significance between normotrophic scars and normal skin (P> 0.0167).3. CD105 expressed mainly on the cell membrane of endothelial cell. Some cell membranes or cytoplasms of basal cells and spinous layer cells are also stained. There was a statistical significance between the Pathologic scars and normotrophic scars or normal skin (P<0.05). There was also a statistical significance between normotrophic scars and normal skin (P<0.05).4. The dependability analysis showed that there was a significant positive correlation between Integrinβ₁ and E2F1 (r=0.426<1) or CD105-MVD (P<0.05). There was a significant positive correlation between E2F1 and CD105-MVD (P<0.05).Conclusions1. The high expression of Integrinβ₁ and E2F1 in Pathologic scar indicated that they can cooperate with some cell factors, protect the fibroblasts from apoptosis and secret cell factors which can generate more matrixes, to promote the development of Pathologic scar.2. The final effect of the Integrins signaling system is to suppress the cell apoptosis. Through a series of signaling, Integrinβ₁ can activate E2F1 by adhesing to FAK and restricting Rb to protect the fibroblasts from apoptosis.3. Vasiformation can promote the formation of Pathologic scar. Integrinβ₁ can promote the generation of microvessel. It can resist the apoptosis of endotheliocyte, promote its proliferation and mediate the migration or the formation of the blood capillary lumens. It also can up-regulate the generation of microvessel by regulate the blood vessel chemotatic factors and growth factors downstream.4. E2F1 also expressed in the endothelial cell, which can promote the endothelial cell proliferation. And this can be one of the reasons that cause capillary vessels occlusive or semi-occlusive. At the same time, it can up-regulate the generation of microvessel.