Expression And Significance Of MTOR/P70S6K Signal Pathway In Pathologic Scars

Objectives:Pathologic scar (PS) mainly includes keloid (K) and hypertrophic scar (HS). The general performance is pain, pruritic, tumor-like growth, even with varying degrees of dysfunction in clinic manifestation. It is ariseed excessive accumulation of extracellular matrix and excessive fibroblast proliferation in histology manifestation, while the proliferation of fibroblasts from excessive or insufficient apoptosis is the important biological foundation for the formation of pathologic scar.Mammalian target of rapamycin (mTOR) is a kind of serine/threonine protein kinase. On the one hand, it can regulate gene transcription, protein translation and cell growth cycle. On the other hand, it is a key factor of signaling pathway of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt/PKB) and the key step of regulation of cell growth. It can activate downstream substrates and exert biological activity. As the direct substrate of mTOR,70-kDa ribosomal protein S6 kinase(P70S6K) can stimulate the ribosome synthesis, accelerate the translation process of mRNA, shorten the cell cycle, and increase the rate of cell growth, so that promot the cell growth. In the past few years, the study of mTOR and its upstream proteins such as PI3K, Akt and other studies confirmed that it plays an important role in the fibroblast proliferation and pathologic scar formation, but the study of the relationship between mTOR/P70S6K signaling pathway and pathological scar is rarely reported. Phosphorylated mTOR and phosphorylated P70S6K (p-mTOR and p-P70S6K) are the activated form of mTOR and P70S6K in vivo, p-mTOR and p-P70S6K expression in the pathological scar were detected for the research with immunohistochemical SP method, and discuss the role of mTOR/P70S6K signaling pathway in the formation of pathological scar role.Materials and methods:The samples were collected from Department of Plastic Surgery, the First Affiliated Hospital of Zhengzhou University from July,2008 to March,2005. There were 20 cases of keloid,9 males and 11 females, aged from 3.5 years old to 25 years old, with the course of disease from 6months to 12 years. The samples were respectively harvested from the ear, chest, armpit, and the left upper limb. There were 20 cases of hypertrophic scar,12 males and 8 females, aged from 7.5 years old to 19 years old, with the course of disease from 9 months to 7 years. The samples were harvested from face and neck, shoulder, armpit and upper limb. There were 20 cases of non-hypertrophic scar,13 males and 7 females, aged from 7 years old to 56 years old, with the course of disease from 11 months to 18 years. The samples were harvested from the face and neck, upper limbs, right leg and right lower abdomen, there were 20 cases of normal skin,11 males and 9 females, aged from 5.5 years old to 46 years old. The samples were harvested from the eyelids, inside upper arm, abdomen and peri-umbilicus, which were remanent at the cosmetic surgery and full-thickness skin graft. All the patients do not have skin diseases, connective tissue diseases, infectious diseases, cancer or other major organ disease, and there was no history of radiotherapy, laser therapy or immunotherapy preoperation. Immunohistochemical SP method was adopt to study the expression of p-mTOR and p-P70S6K in the keloid, hypertrophic scar, non-hypertrophic scar and normal skin tissue, and the relationship between the expression of p-mTOR and p-P70S6K in pathological scar tissue.On the base of the above researches, the experiment data are analyzed with statistical package for the social 16.0(SPSS16.0) software package. The positive rate of tissue protein list was analyzed with x2 inspection and analysis of variance. Study on the relationship between the expression of p-mTOR and p-P70S6K in pathological scar tissue. A value less than 0.05 was considered as significance.Results:1. p-mTOR mainly expressed in the fibroblasts cytoplasm and some nuclei with brownish yellow in pathological scar, a small amount of non-expression in hypertrophic scar. It was expressed occasionally in the normal skin.2. P70S6K mainly expressed in the fibroblasts cytoplasm and some nuclei with brownish yellow in pathological scar, a small amount of non-expression in hypertrophic scar. It was expressed occasionally in the normal skin.3. The p-mTOR expression rate (75.00%) in Pathologic scar tissue was significantly higher than non-hypertrophic scar (20.00%) and normal skin (10.00%), the difference was significant (P< 0.0167)4. The p-P70S6K expression rate (72.50%) in Pathologic scar tissue was significantly higher than non-hypertrophic scar (10.00%) and normal skin (5.00%), the difference was significant (P< 0.0167)5. Correlation analysis showed that p-mTOR and p-P70S6K expression was positively correlated in pathologic scar tissue (r= 0.482, P< 0.05).Conclusions:1. The p-mTOR expression rate in pathological scar was significantly higher than non-pathological scar and normal skin. Its high expression may be through some kind of cell signal transduction pathway to increase energy metabolism, promote protein synthesis and cell hypertrophied, promote fibroblast cell proliferation, inhibit the apoptosis of skin fibroblasts, which plays an important role in the formation and development of pathological scar.2. The p-P70S6K expression rate in pathological scar was significantly higher, which may promote fibroblast cell proliferation by the way of regulating and controlling cell cycle, and ribosome biogenesis. So that it plays an important role in the formation and development of pathological scar.3. p-mTOR and p-P70S6K expression was positively correlated in pathologic scar tissue, which may play a synergistic effect in pathological scar formation and development.