ABSTRACT
BACKGROUND: The polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder with pathological mechanisms remain unclear. The following study investigates the ovarian hyperfibrosis forming via transforming growth factor-ß (TGF-ß) signaling pathway in Dehydroepiandrosterone (DHEA)- induced polycystic ovary syndrome (PCOS) rat model. We furthermore explored whether TGF-ßRI inhibitor (SB431542) decreases ovarian fibrosis by counterbalancing the expression of fibrotic biomarkers. METHODS: Thirty female Sprague-Dawley rats were randomly divided into Blank group (n = 6), Oil group (n = 6), and Oil + DHEA-induced model group (n = 6 + 12). The model groups were established by subcutaneous injection of DHEA for 35 consecutive days. The 12 successful model rats were additionally divided in vehicle group (n = 6) and SB431542-treated group (n = 6). Vehicle group and SB431542-treated group, served as administration group and were intraperitoneally injected with DMSO and SB431542 for additional 14 consecutive days. Ovarian morphology, fibrin and collagen localization and expression in ovaries were detected using H&E staining, immunohistochemistry and Sirius red staining. The ovarian protein and RNA were examined using Western blot and RT-PCR. RESULTS: In DHEA-induced ovary in rat, fibrin and collagen had significantly higher levels, while the main fibrosis markers (TGF-ß, CTGF, fibronectin, a-SMA) were obviously upregulated. SB431542 significantly reduced the expression of pro-fibrotic molecules (TGF-ß, Smad3, Smad2, a-SMA) and increased anti-fibrotic factor MMP2. CONCLUSION: TGF-ßRI inhibitor (SB431542) inhibits the downstream signaling molecules of TGF-ß and upregulates MMP2, which in turn prevent collagen deposition. Moreover, ovarian hyperfibrosis in DHEA-induced PCOS rat model could be improved by TGF-ßRI inhibitor (SB431542) restraining the transcription of accelerating fibrosis genes and modulating EMT mediator.
Subject(s)
Dehydroepiandrosterone/adverse effects , Polycystic Ovary Syndrome/etiology , Polycystic Ovary Syndrome/metabolism , Signal Transduction , Transforming Growth Factor beta/metabolism , Animals , Biomarkers , Disease Models, Animal , Estrous Cycle , Female , Fibrosis , Flow Cytometry , Gene Expression Profiling , Gene Expression Regulation , Hormones/blood , Immunohistochemistry , Polycystic Ovary Syndrome/pathology , RatsABSTRACT
Facial depression is not rare conditions caused by soft tissue loss or bone distortion. In such conditions, autogenous bone, cartilage and bioacceptible materials are used for soft tissue augmentation. De Nicola used silicone rubber implant first in 1950. That after, silicone implants are used for bone defect and soft tissue augmentation. We experienced 31-year-old male patient who injured open depressed fracture of right temporal bone. He was operated with autogenous bone graft for bone defect area and silicone implants for soft tissue augmentation. After about 6 years later, mass palpated in right temporal area. There was no inflammatory sign in physical examination and CT finding. So we removed hyperfibrotic tissue totally with previous inserted silicone implants and augmented soft tissue with pored Medpor(R) block. In light microscopic findings, only tissue hyperfibrosis were proved without inflammatory cell, such as giant cell or ephithelioid cell.
