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Objective: Considering the importance of integrin molecules in the implantation and lack of sufficient information in the expression pattern of these molecules in various phases of estrous cycle. It seemed to be necessary to investigate these molecules in mouse endometrial during the various phases of oestrous cycle. Materials and Methods: Female NMRI mice (n=15) aged 6-8 weeks were studied. Various phases of estrous cycle including: proestrus, estrus, metestrus and diestrus were determined by vaginal smear. The mice were sacrificed (at least 3 per each phase) by cervical dislocation and the tissues were obtained from the middle 1/3 part of their uterine horns at each phase then the cryosections at thicknesses between 8-10 μ were obtained. Then the immunohistochemistry were done for integrins of 4, 1, v, 3 and their ligand osteopontine. Results: The integrins were expressed only in the metestrous phase of oestrous cycle in the different locations of mouse endometrium. The positive reactions were observed for αv, α4 and β3 in the apical and basal membrane of glandular epithelium. Also the positive reaction for β1 was found in surface and glandular epithelium as well as stroma. The osteopontin expression was seen in the apical membranes of surface and glandular epithelium and was not seen in other locations. Conclousion: It seems that expression of integrins in endometrium is based on their role in the implantation, therefore the molecules α4, β1 and OPN that are expressed on the surface epithelial may be involve in the adhesion of cell to cell and integrins of αv, β3 that are expressed in the glandular

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Integrin inhibitors may change conformational and dynamical properties of integrin, but its molecular properties in this process is not clearly understood. Tumstatin is an anti-angiogenesis protein derived from collagen XVIII, but little is known about how tumstatin applies its antiangiogenic and antitumor effects. It has been reported that 18 amino acids fragment of tumstatin has anti-tumor activities similar to tumstatin. We used molecular docking and molecular dynamic simulations to describe inhibitor activity of peptide in molecular level. We described the binding of this peptide to Hybrid/EGF-4 interface and that these interactions might contribute to improved hydrophobic interactions at these regions and also fixed the mobile domains of integrin. In the complex, we recognized a novel binding site on integrin for integrin inhibitors that may have critical role in integrin inhibition. These results support the idea that hydrophobic interactions between Hybrid/EGF-4 domain and peptide-anti tumor might contribute to stability of bended state and therefore inhibit integrin activation.  Our finding can be applied to understand the mechanism of out-in pathway integrin signaling and development of integrin targeted drug.