Figure 6.
(A). The small GTPases serve as molecular switches to regulate signal transduction pathways. The input induces GEFs activation, facilitating the conversion from inactive GDP-bounded configurations to active GTP-bound configurations. While GAPs mediate the hydrolysis of GTP, leading to the inactivation of the small GTPases. (Created with BioRender.com). (B) (a) The mRNA expression for connective tissue growth factor (CTGF), alpha smooth muscle actin (ACTA2), and collagen (COL1A2) are quantified by qPCR (96). All those fibrotic markers are up-regulated in SSc-patient dermal fibroblasts compared to normal human dermal fibroblasts (96). (b) CCG-203971 treatment reduces the expression of CTGF, ACTA2, and COL1A2. Before mRNA isolation, SSc dermal fibroblasts were treated for 24 hours in the presence of the indicated concentration (mM) of CCG-203971 or 300 mM PFD (96). Data are mean 6 S.E.M. of samples from at least four individuals. (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 versus DMSO control.) (96) (C). CCG-203971 prevents bleomycin-induced fibrosis in vivo. (***P<0.001, ****P<0.0001.) (96).