Expression Of Focal Adhesion Kinase, Phosphor-protein KinaseB And Nuclear Factor κB In Pathologic Scar Tissue

Pathologic scar is a particular fibro-metabolic disease of derma in human being which is characterized by excessive proliferation of fibroblasts and accumulation of collagen together with other extracellular matrix. It results from wound, infection, and burns etc. It includes hypertrophic scar and keloid. The clinical characteristic involve dysaesthesia, tumor-like growth and a certain extent functional impediment etc. Pathogeny and etiopathogenesis of pathologic scar are still unclear and the therapy is a medical difficult problem for surgery.Along with the development of cellular biology and molecular biology and it gets into the investigate realm of scar, The turbulence of proliferation or apoptosis of fibroblasts, Unbalance of synthesis or degradation of collagen, A great deal of creation of cytokines and the affinity among the above three factors constituted the biological foundation of pathologic scar. It is still a groping focus to investigate the biological behaviour of fibroblast in pathologic scar in the field of studying the formation of pathologic scar at present. The interaction of extracellular matrix and fibroblasts render magnanimous proliferation of fibroblasts in fibro-metabolic disease, and the significance already revoke attention.Focal adhesion kinase(FAK) is dissociative siginal transmitting molecule in the cytoplasm of fibroblsts. It mainly participate in the integrin mediated signal conduction pathway. Integrin activate FAK, sequencely enter Phosphatedylinositol -3-kinase (PI3K) pathway. As the direct target protein, Protein kinase B (PKB) operate a key function in the signal pathway. PKB becomes phosporylated Protein kinase B(P-PKB) after being activated, and has many functions such as accelerate cell proliferation,prevent cell apotosis, Promote the compound of protein and hepatin, Adjust cell cycle and so on. NFκB is the backword position signal protein of P-PKB. NFκB lie in cytoplasm and enter into karyon after it is activated. Regulating the expression of many genes.Study have showed that the development of pathological scar closely correlate with overexpression of integrin in the surface of fibroblasts. PI3K signal pathway is one of the integrin mediated signal pathway. Integrin activate FAK, Sequensely enter PI3K pathway. The contribution of integrin mediated signal pathway have witnessed in the development of tumor. There are overexpressive integrin in both tumor matrix and pathological scar. It is feasible to investigate the expression of integrin signaling kinase in pathological scar, Together with the relationship the development of pathological scar. It will help to reveal the developed mechanism of pathological scar and provide theoretic base for preventing and treating pathologic scar.So we adopt immunohistochemical methods (SP technique) to detect separately FAK, P-PKB and NFκB in 40 pathologic scar cases, 20 normotrophic scar cases and 20 normal skin cases. The ralationship between the expression of FAK and P-PKB or NFκB in 40 pathologic scar cases were also analyzed. The study may reveal the correlation between the expression of integrin signaling key kinase and the formtion of pathological scar. It will provide theoretic base for preventing and treating pathologic scar in the new way.Materials and methodsTissue specimens of pathologic scar and normotrophic scar were obtained from the patient who were underwent plastic surgery in the first affiliated hospital of zheng zhou university etc. Tissue specimens were collected from face, neck, chest, and limbs etc. Tissue specimens of Normal skin were acquired in the operation of skin transplantation, Tissue specimens were collected from limbs, abdomen, and back etc. All tissue specimens were required to accord with the principles: Detailed case history and feedback record; Therapy out of radiation, laser, or immunity; The pathologic confirmation. The number of pathologic scar, normotrophic scar and normal skin tissues are 40, 20, and 20. The immunohistochemical methods (SP technique) were used to detect the function and expression of FAK, P-PKB and NFκB in pathologic scar, normotrophic scar and normal skin cases. The relationship between the expression of FAK and P-PKB or NFκB in pathologic scar cases were also systematically analyzed. The statistical analysis were executed by SPSS 13.0 software. P values less than 0.05 are considered significant.Results1. The expression of FAK protein in pathologic scar, normotrophic scar and normal skin tissuesThe positive expression were mainly localized in the cytoplasm of epidermal fundus cells and blood vessel endodermis cells in normal skin tissues. The positive expression were also localized in the cytoplasm of most fibroblast besides this in the collagen knur or swirl configuration of pathologic scar tissues beside above cells. The positive rate was 65.00% (26/40) in the pathologic scar tissues, 35.00% (7/20) in normotrophic scar and 25.00% (5/20) in normal skin tissues. Compare with normotrophic scar and normal skin cases, The expression of FAK protein were significant different in pathologic scar cases(P<0.05). But there were no significant difference in the expression of FAK protein between the normotrophic scar and normal skin cases (P>0.05).2..The expression of p-PKB protein in pathologic scar, normotrophic scar and normal skin tissuesThe positive expression of p-PKB protein were mainly localized in the cytoplasm. In pathologic scar, the positive signal were mostly concentrated in the fibroblast of collagen knur or swirl configuration and other positive signal lied in parts of the blood vessel endodermis cells and fundus cells. The positive rate was 67.50% (27/40) in the pathologic scar tissues, 40.00% (8/20) in normotrophic scar and 20.00% (4/20) in normal skin tissues. Compare with normotrophic scar and normal skin cases, The expression of p-PKB protein were significant different in pathologic scar cases (P<0.05). But there were no significant difference in the expression of p-PKB protein between the normotrophic scar and normal skin cases (P>0.05).3. The expression of NFκB protein in pathologic scar, normotrophic scar and normal skin tissuesThe positive expression were mainly localized in the cytoplasm or karyon of epidermal fundus cells and blood vessel endodermis cells in normal skin tissues. The positive expression were also localized in the cytoplasm or nuclei of most fibroblast in the pathologic scar tissues besides above cells. The positive rate was 72.50% (29/40) in the pathologic scar tissues, 40.00% ( 8/20) in normotrophic scar and 35.00% (7/20) in normal skin tissues. Compare with normotrophic scar and normal skin cases, The expression of NFκB protein were significant different in pathologic scar cases (P<0.05). But there were no significant difference in the expression of NFκB protein between the normotrophic scar and normal skin cases (P >0.05).4. The correlation analyse of the expression of FAK, p-PKB and NFκB proteinThe results of analysis of correlation of the expression in the pathologic scars group indicate that the expression of FAK has significant correlation with that of p-PKB, and the expression of FAK has significant correlation with that of NFκB (P<0.05). The expression of P-PKB still has significant correlation with that of NFκB (P<0.05).Conclusion1 The expression of FAK protein are significant different in pathological scar ,Compare with normotrophic scar and normal skin cases. It show that FAK may promote the proliferation of FBS,and inhibit the aopotosis of that.and take important role in the formation of pathlogical scar.2. Protein PKB is the expression production of oncogene c-akt. P-PKB is the activative formation of PKB. The expression of P-PKB protein are significant different in pathological scar, Compare with normotrophic scar and normal skin cases. It's may contribute to proliferation,differentiation and apoptosis of fibroblasts and may participate in the regulation of cytokines. result in the abnormal proliferation of fibroblasts in the pathologic scars.3. The up-regulation of NFκB in the pathologic scar suggests that the NFκB may promote the proliferation and inhibit the apoptosis of fibroblasts and blood vessel endodermis cells. The NFκB may correlate with the formative mechanism of pathologic scar.4. The expression of FAK has significant correlation with that of NFκB and P-PKB. The expression of FAK, PKB and NFκB might play synergetic roles in the process of forming of pathologic scar.