Epidermal growth factor receptor（EGFR）trans activation is a critical element in G-protein coupled receptor agonist-induced mitogenic signaling in various cells. We have recently reported that the trans activation plays a role in the slgnaling process leading to angiotensin II（Ang II）- and endothelin-1（ET-1)-induced proliferation in cultured rabbit gingival fibroblasts（CRGF). TGF-αis a potent mitogen structurally and functionally related to EGF and interacts with EGFR. In the present study，we investigated whether TGF-α contributes to EGFR trans activating process leading to Ang II- and ET-1-induced proliferation of CRGF. The Ang II and ET-1 induced proliferation were inhibited by TAPI-2，an inhibitor of TGF-α shedding. Expression of TGF-α protein was detected and abolished by TAPI-2 pretreatment in the CRGF stimulated by Ang II- and ET-1.TGF-αinduced proliferation of CRGF. The proliferation was inhibited by PD153035，a selective inhibitor of EGFR trans activation．These findings suggest that TGF-α contributes to EGFR trans activation leading to Ang II- and ET-1-induced proliferation in the CRGF.
P3L-34
