Chemokine and Peptide Derivatives for Would-Healing, Fibrotic Disease Treatment, and Tumor Supression
A University of California researcher has characterized an avian chemokine that acts both directly and as an agent for various growth factors in wound-healing. The gene that encodes this protein is an inducible chemokine gene that is expressed at low levels in tissue of mesenchymal origin, but is expressed at high levels shortly after wounding and persists throughout the period of granulation tissue formation. It is also highly expressed in tissue surrounding tumors induced by Rous-sarcoma virus. Thrombin is the most potent natural stimulator of this gene, and the resulting protein is chemotactic for monocytes and lymphocytes in vivo and is angiogenic.
The very rapid stimulation by thrombin, coupled with the fast synthesis of the UC gene product, suggests that it is a new type of stress protein whose production is geared towards protecting tissues rather than individual cells. These results point to the possibility of novel therapeutic procedures based upon the UC gene product, its derivatives, and/or their mammalian homolog(s) for enhancing wound healing and for tumor suppression, possibly with decreased development of scar tissue.
Characterization of various polypeptide fragments of the UC chemokine has led to further important discoveries. One non-angiogenic fragment stimulates the differentiation of fibroblasts to myofibroblasts, which could serve as the basis for pharmaceutical agents for inducing or inhibiting myofibroblast formation in vivo or in vitro, and for screening other agents for their ability to modulate myofibroblast differentiation. Since myofibroblast differentiation plays a critical role in wound healing and is implicated in a number of fibrotic diseases, this fragment could have considerable therapeutic significance.
Another fragment of this chemokine has been found to have angiogenic properties, including chemotaxis for blood vessels and vessel sprouting, but is devoid of chemotactic activity for leukocytes. This chemokine fragment could be useful for inducing blood vessel formation without attracting leukocytes, thus avoiding the granulation-like tissue formation often associated with angiogenesis (e.g. scar formation). This too could have important implications for wound-healing and for screening for angiogenic and angiostatic agents.
US 6,962,971 [MORE INFO
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