oblem to which no efficacious treatments currently exist. Thus, understanding the complexity of the healing process is critical to resolve patient problems. In physiological remodeling, such as during dermal wound healing, fibroblast activation finishes when tissue is repaired, and activated fibroblasts disappear by apoptosis. However, in pathological wound healing activated fibroblasts persist and leads 17016504 to fibrosis and tissue deDHMEQ manufacturer formation, which is evident in hypertrophic scars in the fibrotic phase of scleroderma, after burn injury and in fibrosis of vital organs such as liver, heart and lung. Different cells types and numerous growth factors are involved in each phase of wound healing. Among them, transforming growth factor beta and its receptors, including endoglin, are essential in this process. TGFb plays a critical role in different phases of wound healing by regulating production of extracellular matrix, proteases, chemotaxis, migration and proliferation 
of different cell types which regulate scar contraction, angiogenesis, granulation tissue formation, ECM remodeling and scar maduration. Endoglin is a type III co-receptor for the TGFb receptors: TbRII, ALK1 and ALK5. Endoglin is expressed in a number of cell types including endothelial cells, monocytes, tissue macrophages, stromal cells, fibroblast, etc… and modulates TGFb dependent responses. Mutations in the endoglin gene can lead to hereditary hemorrhagic telangiectasia and defective angiogenesis. Endoglin, in combination with TGFb family members, plays an important role in regulating different cellular functions such as endothelial cell adhesion, migration and proliferation. Several authors have described endoglin upregulation in different fibrotic 11606371 processes. Thus, endoglin expression is increased in cutaneous scleroderma fibroblasts, liver fibrosis, fibroblasts isolated from strictures in Crohn’s disease or cardiac fibroblasts developing fibrosis. Several studies show that endoglin counteracts TGFb1-dependent responses, such as increased expression of extracellular matrix components, including PAI-1, collagen and fibronectin. It has been described that endoglin could exert this antifibrotic role modulating TGFb1 signaling through pro-proliferative ALK1-Smad1/5 pathway instead pro-fibrotic ALK5-Smad2/3 pathway. These results have been confirmed in cultured fibroblasts as endoglin overexpression leads to a diminution of ECM proteins expression. However, some controversy exists as other authors have described profibrotic effects of endoglin expression. These results suggest that the specific role of endoglin depends on the cell type, environmental conditions or the fibrosis model assessed. Nevertheless the importance of the study of the role of endoglin in fibrotic processes is clear. To evaluate whether endoglin might be involved in post-wound healing fibrosis, we used endoglin-heterozygous mice, since mice lacking endoglin die from cardiovascular defects at mid-gestation. To investigate the mechanism of action of endoglin, we assessed the response of endoglinheterozygous mice and dermal fibroblasts derived from them to wounding both in vivo and in vitro. Our results revealed that endoglin acts as an essential component for the accurate completion of tissue repair by its ability to decrease the number of fibroblasts in wounds through its capacity to block Akt activation. 2 Endoglin Regulates Dermal Fibroblast through Akt Histology and immunohistofluorescence For histologica
