Abstract
Abstract: :
Purpose:A major complication after trabeculectomy surgery consists in postoperative scarring with consecutive therapeutic failure. The cytokine transforming growth factor ß (TGFß) plays a pivotal role in wound healing and scar formation. In our investigation, we focus on intracellular signalling mechanisms activated by TGFß in human tenon fibroblasts. Moreover, we were interested in the myofibroblast transdifferentiation process, an important step in ocular wound healing, and went to characterize signalling pathways involved in this process. Methods: Primary human tenon fibroblast cultures were incubated with growth factors of the TGFß superfamily in different concentrations for various time intervals. Activation of the SMAD signalling pathway and MAPK signalling cascades was examined by western blot using phosphospecific antibodies. TGFß effects on fibronectin and α smooth muscle actin (SMactin) were analysed on transcritpion level using RT PCR and on translational level by western blot. Using specific inhibitors, we investigated which signalling cascades are involved in the myofibroblast transdifferentation process. Results: Incubation of fibroblasts with TGFß isoforms resulted in an activation of SMAD and MAPK signalling pathways in a time and dependent manner. Stimulation of human tenon fibroblasts for 3 days with TGFß isoforms increased fibronectin and SMactin levels. Te p38 inhibitor SB203580 reduces TGFß mediated SMactin induction Conclusions: TGFß is a pivotal cytokine in ocular wound healing. It stimulates SMAD and MAPK signalling cascades in human tenon fibroblasts, the major cellular mediator of conjunctival wound repair. We show that the conversion of fibroblast to myofibroblast induced by TGFß isoforms can be blocked by the p38 inhibitor SB203580. Specific modulation of the myofibroblast transdifferentiation process may provide a new approach to prevent postoperative scarring.
Keywords: wound healing • signal transduction