ANTIBODIES TO POLYPHOSPHATE DECREASE FIBROSIS
Polyphosphate activates the intrinsic pathway of coagulation that also induces inflammation. Hypercoagulable and hyperinflammatory challenge are mediators contributing to endothelial dysfunction, organ failure and death, which occur in many pathological conditions. Upon platelet activation, Polyphosphate is released into the microenvironment, where it has been shown to promote coagulation and act as a proinflammatory molecule. The inventors have found that platelet- sized polyphosphate promotes migration of fibroblasts, and also induces smooth muscle actin expression and the formation of stress fibers in fibroblasts, both of which are hallmarks of myofibroblast differentiation. Myofibroblasts play roles in driving both wound healing and fibrosis. This work suggests that polyphosphate not only promotes early wound healing through enhancing fibrin clot formation, but also may play a role in the later stages of wound healing and potentially the progression of fibrotic diseases by recruiting and inducing the differentiation of fibroblasts into myofibroblasts. As such, polyphosphates can be targeted by inhibitors for the treatment of aberrant/pathologic fibrosis, such as anti-polyphosphate antibodies and polyphosphatase enzymes, as well as used as biomarkers for diagnosis, prognosis, and treatment response indicators to provide guidance for treatment plans.