Ischemia Regulates Endoglin Expression in a Pig Skin Flap Model

Abstract

Endoglin is a transmembrane protein that binds transforming growth factor b (TGF-b) with high affinity. It is thought to modulate TGF-b signaling and responses through interactions on cell surfaces with TGF-b receptors. It is highly expressed on endothelial cells of tissues undergoing angiogenesis. Since ischemia-induced changes such as angiogenesis are in part regulated by TGF-b, it is important to elucidate the precise mechanism by which they occur if we are to influence the effects of ischemia on tissue. Since endoglin is one of the receptors involved in regulating TGF-b signaling, we tested whether endoglin expression will increase in response to ischemic injury. A pig skin flap model was developed and used in our laboratory to study the effect of ischemia on the expression of endoglin and its ligand TGF-b1 using immunohistochemistry. We observed an increased expression of endoglin and TGF-b1 in the epidermal layer, blood vessels, and fibroblasts in ischemic skin flaps as compared to non-ischemic control skin flaps. Given the role of TGF-b and endoglin in angiogenesis, this may represent a mechanism by which ischemia stimulates angiogenesis. Much work remains to be done to delineate the exact mechanisms by which TGF-b acts and the exact role of endoglin in TGF-b signaling. Understanding how to regulate the actions of TGF-b by manipulating the expression of endoglin may provide a therapeutic avenue given the importance of TGF-b in tumour angiogenesis.