Role of Growth Factors in the Development of Lymphangiogenesis Driven by Inflammatory Bowel Disease: A Review

Studies on angiogenesis and lymphangiogenesis have gained special relevance in research into factors potentially influencing the pathogenesis and course of inflammatory bowel disease (IBD). The results of the few existing studies on the distribution and density of lymphatic vessels and blood vessels in the context of IBD are controversial. Studies using the specific lymphatic marker podoplanin have revealed a significantly large number of lymphatic vessels in the colonic mucosa of patients with ulcerative colitis and Crohn's disease (compared to patients with normal mucosa), whereas other authors have found no significant differences. However, the role of vascular endothelial growth factor (VEGF) tyrosine-kinase receptor 3 (VEGFR-3) in the onset of IBD has not been analyzed. In recent years new biochemical, molecular, and immunohistochemical studies indicate that several families of growth factors, such as the VEGF family and their receptors, fibroblast growth factor-2, platelet-derived growth factor-BB, hepatocyte growth factor, the angiopoietin system, and integrins may play an important role in the onset of IBD. To date, no comparative studies have analyzed these growth factors and specific lymphatic markers. We examine how growth factors are involved in the development of pathological lymphangiogenesis in patients with IBD and determine whether they play a crucial role in disease exacerbation.