VEGF is produced by various cells, such as hepatocytes, tumor cells, smooth-muscle cells, osteoblasts, and pericytes around vascular endothelium, keratinocytes, and human dental pulp cells. It has been reported that VEGF is produced in response to various components of pathogenic bacteria in periodontal tissues within vascular endothelial cells, plasma cells, and macrophages and in junctional, sulcular, and gingival epithelium. VEGF is also detectable in human gingival fibroblasts and human periodontal ligament fibroblasts.
Several mechanisms are known to have a role in the regulation of VEGF gene expression. Hypoxia is the main stimulus for increased VEGF expression both in vitro and in vivo. VEGF mRNA expression has also been shown to be upregulated by some types of cytokines and growth factors. Thus IL-6 significantly induces VEGF in several cell lines. In fibroblastic and epithelial cells VEGF can be upregulated in response to TGF-a. In vascular smooth muscle cells basic fibroblast growth factor induces the expression of VEGF. Other types of cytokines upregulating VEGF expression include IL-10, PGE2, and TGF-a.
In addition, alterations in cellular regulatory pathways may result in VEGF upregulation. For example, VEGF mRNA is upregulated during the myogenic differentiation of C2C12 cells and during the conversion of 3T3 preadipocytes into adipocytes. Specific transformation is another event that can result in VEGF gene expression induction. This could include oncogenic mutations of ras, mutation of the murine p53 tumor suppressor gene, and overexpression of v-raf.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.