Proteases Potentiate Fibrocyte Differentiation
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45% of deaths in the United States involve fibrosing diseases and the treatment of non-healing chronic wounds costs more than $25 billion annually in the United States alone. Scar tissue formation plays a critical role in both wound healing, and fibrosis. Currently, there is not a solid understanding of the mechanism that triggers initiation of scar tissue formation in healing wounds and fibrosing diseases such as chronic kidney disease, scleroderma, chronic asthma, and idiopathic pulmonary fibrosis. Fibrocytes are fibroblast-like cells involved in the formation of scar tissue in healing wounds and fibrosing disease. The time required to form scar tissue in a wound is related to the amount of fibrocytes present. As fibrocyte differentiation increases, scar tissue forms faster; however, if fibrocyte differentiation is hindered, then scar tissue takes longer to form. Thrombin and tryptase are proteases involved in both wound healing and fibrotic lesions, while trypsin has been used topically to speed wound healing. Adding trypsin, thrombin and tryptase to PBMC isolated from donor’s blood increases the amount of fibrocyte differentiation, suggesting that these proteases play a critical role in the potentiation of fibrocyte differentiation. In addition to potentiating fibrocyte differentiation, these proteases also increase the proportion of M2a pro-fibrotic macrophages as well as collagen production, both makers for scar tissue formation. Fibrocyte differentiation is greatly inhibited by the presence of the plasma protein Serum Amyloid P (SAP). Tryptase and thrombin potentiate fibrocyte differentiation in the presence of SAP, suggesting that these proteases can be part of a triggering mechanism for scar tissue formation in both healing wounds and fibrotic lesions. Consequently, proteases may be an effective treatment for non-healing wounds, and protease inhibitors could be an effective treatment for fibrosing diseases. .
Galvis Carvajal, Elkin David (2014). Proteases Potentiate Fibrocyte Differentiation. Honors and Undergraduate Research. Available electronically from