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Expression of Focal Adhesion Kinase, Phosphor-protein KinaseB and Nuclear Factor κB in Pathologic Scar Tissue

Author: LiuYuLi
Tutor: WangXiMei
School: Zhengzhou University
Course: Surgery
Keywords: Integrin Focal adhesion kinase Phosphorylation of protein kinase B Nuclear factor KB Pathological scar
CLC: R622
Type: Master's thesis
Year: 2007
Downloads: 92
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Abstract

Pathological scar (pathologic scar, PS) is abnormal dermal injury after tissue repair. It occurs in trauma, infections, burns, as the excessive proliferation of fibroblasts (fibroblast, FBs) and the extracellular matrix (extracellular matrix, ECM)'s is characterized by excessive deposition. Clinical manifestations of pain, itching, and tumor-like hyperplasia and with varying degrees of dysfunction. The pathological scar etiology and pathogenesis is not yet clear, is currently no effective treatment. In recent years, with the in-depth study of modern cell biology and molecular biology in the field of scar, so as to further understanding of the biological basis of pathological scar repair cells: (FBs) proliferation inhibitor of apoptosis, ECM in collagen synthesis and degradation of imbalance, the close relationship between some cytokines Its three. The pathological scar FBs biological behavior focus is to explore the pathogenesis signal pathway activation has raised concerns the significance of the FBs proliferation in fibrotic diseases. Focal adhesion kinase (focal adhesion kinase, FAK) is a non-receptor protein tyrosine kinase, is mainly involved in the integration-mediated signal transduction. Integrin activation of FAK into phosphatidylinositol 3 - kinase (phosphatedylinositol-3 kinase, PI3K/AKT) pathway. Protein kinase B (protein kinase B, PKB) as the PI3K pathway directly target protein plays a key role in the signaling system, the phosphorylation of protein kinase B (phosphor-protein kinase B, P-PKB) its activated form, promote cell proliferation, the cells against apoptosis, regulate the cell cycle and other biological functions. Nuclear factor κB (nuclear factorκB, NF-κB) is a multi-directional regulation of transcription factor, plays a critical role in the regulation of the expression of many genes in the cell. PKB in downstream signaling proteins in the external signal stimulation, inhibition of protein IκB degradation, NF-κB dissociation from its complex to enter the nucleus, with the specific DNA sequences in the nucleus, to play its transcriptional regulation. Studies have shown that overexpression is closely related to the development of pathological scar FBs surface integrin. PI3K is one of the integrin-mediated signal transduction pathway, integrin-mediated PI3K pathway in tumor development has been confirmed. Overexpression of integrin-associated tumor stroma and pathological scar. Research PI3K pathway in pathological scar expression and pathologic scar relationship of development, will help to reveal the mechanism of pathological scar, and provide the basis for the prevention and clinical treatment. The subjects using immunohistochemical staining techniques to explore of FAK, P-PKB and NF-κB in pathological scar, non-pathological scar and normal skin in the expression of their mutual relations, designed to reveal the PI3K pathway and pathologic scar formation relationship, in order to provide new ideas for the prevention and treatment of pathological scars. Materials and Methods orthopedic surgical resection of pathological scar, non-pathological scar drawn parts of the face, neck, chest or limbs. Normal skin taken from the full-thickness skin graft donor site skin drawn parts of the limbs, abdomen or back. All specimens have detailed a complete medical history and follow-up record, none of the line radiation therapy, laser therapy or immune confirmed by pathology. Keloids of 10 cases, 30 cases of hypertrophic scars pathological scar group, including 22 males and 18 females, aged 2 ~ 65 (20.8 ± 9.1) years, duration of 0.6 ~ 6.0 (2.3 ± 1.4) years; non-pathological the scar 20 cases, 10 males and 10 females, aged 3 ~ 50 (21.5 ± 11.3) years, duration of 0.5 ~ 5.0 (2.3 ± 1.6) years; normal skin of 20 patients, 12 males and 8 females, aged 2 to 64 (23.5 ± 11.6) years old. This topic using immunohistochemistry technique (SP), were detected the PI3K pathway FAK, p-PKB and NFκB in pathological scar expression in non-pathological scar and normal skin, and explore in pathological scar FAK, p-PKB and NF-κB expression of mutual relations. The measured data with SPSS13.0 software package for statistical analysis, α = 0.05 level of inspection. Results 1. FAK protein immunohistochemistry results in pathological scar collagen nodules, most of the FBs cytoplasmic staining of swirling structure, the positive expression rate was 65.00% (26/40). Non-pathological scar tissue part FBs cytoplasmic lighter coloration, the positive expression rate was 35.00% (7/20). Normal skin tissue FBs FAK protein expression was 25.00% (5/20). Pathological scar and non-pathological scar, normal skin, the difference was statistically significant (P <0.05). Non-pathological scar and normal skin was no significant difference (P> 0.05). 2. p-PKB protein immunohistochemistry results of pathological scars p-PKB expression in FBs cytoplasm, positive signals were mainly concentrated in the the collagen nodule, swirling structure, the positive expression rate of 67.50% (27/40). Part of the vascular endothelial cells and skin basal cell cytoplasm also be positive. Part of the expression in non-pathological scar FBs cytoplasm, the positive expression rate of 40.00% (8/20). Mostly lack of expression in normal skin, the positive expression rate of 20.00% (4/20). Pathological scar and non-pathological scar, normal skin, the difference was statistically significant (P <0.05). Non-pathological scar and normal skin was no significant difference (P> 0.05). 3. The NF-κB protein immunohistochemistry results NF-κB in the cytoplasm and / or nuclear staining showed a brownish-yellow as positive signs. Pathological scar collagen nodules, most of the FBs in the the swirling structure in the nucleus or / and cytoplasmic staining of positive expression rate was 72.50% (23/40). Most of the vascular endothelial cells and basal cells will also be positive. Some non-pathological scar tissue FBs cytoplasm and / or nucleus positive, positive expression rate was 40.00% (8/20). NFκB protein was located in a small part of FBs epidermal basal cells, capillary endothelial cell cytoplasm and / or nucleus, of FBs positive expression rate was 35.00% (7/20) in normal skin tissue. Pathological scar and non-pathological scar, normal skin, the difference was statistically significant (P <0.05). Non-pathological scar and normal skin was no significant difference (P> 0.05). 4. FAK expression and p-PKB, NF-κB expression correlation analysis of pathological scar group FAK expression and protein expression of p-PKB and FAK protein expression and NFκB protein expression, FAK expression and NF-κB protein expression were positively correlated sex (P <0.05). Conclusion 1. FBs cytoplasmic FAK in pathological scar showed high expression, suggesting that some cytokines (TGF, PDGF, etc.) may stimulate the the FBs surface integrin expression and local FAK tyrosine phosphorylation and activation, FAK activation downstream signaling conduction (Ras / MAPK pathway, PI3K pathway), promote the abnormal proliferation of FBs involved in pathological scar formation. 2. p-PKB upregulated in pathological scar, likely through the activation of a variety of factors involved in the differentiation of FBs proliferation or regulation of cytokines inhibited apoptosis, promote pathological scar formation. 3. NF-κB is highly expressed in pathological scar may prevent the DR pathway of apoptosis protein bcl-2, C-myc, Cyclin D1 gene expression by promoting promote inhibition of death receptor (DR) pathway of apoptosis gene transcription, raised interfere with the transcription of the p53, and the inhibition of p53-induced apoptosis. Promote fibroblast proliferation, inhibition of apoptosis, may play an important role in the formation of pathological scars. 4. There was a positive correlation between the expression of FAK, p-PKB and NF-κB in pathological scar. FAK, p-PKB and NF-κB expression by positive feedback regulation synergy, stimulate excessive proliferation of FBs inhibited apoptosis. Play an important role in the formation of pathological scars.

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