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Figure 5. Rho signalling in radiation-induced intestinal toxicity. (a) The Rho/ROCK pathway controls the molecular signals involved in the development and maintenance of fibrosis including differentiation of smooth muscle cells and subepithelial myofibroblasts, connective tissue growth factor (CTGF) expression and extracellular matrix (ECM) synthesis. (b) In addition, the Rho/ROCK pathway controls acute radiation-induced pathogenic events including inflammation and vascular damage that might contribute to the initiation of late intestinal toxicity. Rho/ROCK pathway pharmacological inhibitors are available. By inhibiting HMG-CoA reductase, the statins inhibit cholesterol synthesis and prevent the formation of isoprenoid intermediates, thus inhibiting Rho translocation to the membrane and subsequent activation. Statins simultaneously inhibit pathways mediated by other G proteins (Ras, Rac). In contrast, ROCK inhibitors (Y-27632) selectively inhibit ROCK activity in a competitive manner with adenosine triphosphate (ATP).
