الفهرس 
Systemic sclerosisOnly 14 pages are availabe for public view
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Abstract
Summary and Conclusion Systemic sclerosis is a fibrotic condition characterized by immunologic abnormalities, vascular injury, and increased accumulation of extracellular matrix (ECM) proteins in the skin. Although the etiology of scleroderma has not yet been fully elucidated, a growing body of evidence suggests that ECM overproduction by activated fibroblasts results from complex interactions among endothelial cells, lymphocytes, macrophages, and fibroblasts, via several mediators and signaling pathways, such as cytokines, chemokines, transforming growth factor beta (TGF-β), toll like receptor 4 (TLR4), IL-6/Signal transducers and activators of transcription (STAT3) signaling and Notch pathway. Numerous experimental animal models for SSc have been established, among which the bleomycin induced SSc model has been widely used because of its ease of handling and applicability to most mouse strains. Bleomycin is a chemotherapeutic agent; however, it also has a profibrotic effect. Repeated subcutaneous injection of bleomycin in mice can induce dermal and pulmonary fibrosis resembling SSc. The Notch signaling pathway is a major regulator of cell-fate determination during development and cellular differentiation. It controls a variety of processes, involving cell fate specification, differentiation, proliferation, and survival. The binding of the ligand to its cognate receptor initiates metalloproteinase-mediated and γ - secretase–mediated proteolysis of the receptor. The Notch intracellular domain (NICD) is then cleaved from the plasma membrane and translocates into the nucleus where it associates with transcription factors CBF1/Su(H)/Lag-1 (CSL) and mastermind-like-1 to form a heteromeric complex and induce changes in gene expression. The