Transforming Growth Factor β/Smad Signal Transduction System In Peritoneal Adhesion Formation Of Endometriosis

Background:PAF(Peritoneal Adhesion Formation) is a very important feature of endometriosis (EM). At present its mechanism is not quite clear. Peritoneum is constructed of the topical monolayer PMCs(Peritoneal mesothelial cells) and the connective tissue. PAF bases on healing disfunction of PMCs, degradation of extracellular matrix, and growth of fibroblasts after peritoneum injury, accompanied with functional disorder of fibrinolysis system. The Transforming Growth Factor β (TGF-β) family participate in the process of healing and PAF after peritoneum injury. The TGF-β family includes three subtypes, which have similar functions and effect each other. TGF-β1play an important role in the process of adhension, while TGF-β3could down regulate the expression of TGF-β1. To regulate the level of TGF-β1or its signaling molecules such as smad3and Smad7may block tissue fibrosis induced by TGF-β. It has been discovered that TGF-β1expresses in stroma cells and infiltrative macrophages in endometriotic ovary-cyst and epitheliums in eutopic endometrium.Objective:1. To investigate microstructure changes in EM.2. To investigate the difference of TGF-β/Smad expression levels between the EM group and control group.3. To investigate the difference of tPA, uPA, PAI-1expression levels between the EM group and control group.Method:1. To observe the microstructure of peritoneum from EM group and control group with HE staining and Masson staining.2. To detect the expression level of TGF-β1, TGF-β3, Smad3and Smad7of PMCs from EM group and control group with immunohistochemistry and Real-Time PCR methods. 3. To detect the expression level of tPA, uPA, PAI-1of PMCs from EM group and control group with immunohistochemistry method.Result:1. In EM group, Enlargement of nucleus of PMCs, thickening of connective tissue, distributive disorder of fiber, increasing of fibroblast and inflammatory cells is observed.2. In PMCs from EM group, TGF-β1and TGF-β3level is up-regulated; GnRHa may down-regulated TGF-β1and up-regulate TGF-β3level.3. In PMCs from EM group, Smad3and Smad7level is up-regulated; GnRHa may down-regulate Smad7level significantly, but no significant effect is found in regulating Smad3.4. In PMCs from EM group, tPA, uPA, PAI-1level is up-regulated. GnRHa may up-regulate tPA and down-regulated uPA level, but no significant correlation to PAI-1level.Conclusion:1. The alteration of microstructure in Peritoneum from EM patients may be conducive to PAF.2. In PMCs from EM group, the alteration of TGF-β/Smad level may be conducive to PAF; GnRHa may inhibit PAF by regulating TGF-β/Smad level.3. In PMCs from EM group, the up-regulating of tPA, uPA, PAI-1may be response to peritoneal injury; GnRHa may promote fibrinolysis by regulating fibrinolysis correlation factor.