MT-100, a human Tie2 agonist antibody, significantly improves penile neurovasculature in diabetic mice via novel target Srpx2
Diabetes is an incurable, long-term, chronic disease that can lead to a variety of complications, including angiopathy, peripheral neuropathy, kidney disease, erectile dysfunction (ED), and infections. The angiopoietin-Tie 2 signaling pathway plays a critical role in blood vessel development, formation, remodeling, and peripheral nerve regeneration. Therefore, activation strategies of the Tie2 signaling pathway have been developed as potential therapies for ischemic and inflammatory vasculoneural diseases. Here, we developed a human Tie2 agonist antibody (MT-100) that not only resists Angpt2 antagonism and activates Tie2 signaling, but also regulates a novel target, Sushi Repeat Containing Protein X-Linked 2 (Srpx2), to survival of vascular and neuronal cells, reduces the production of reactive oxygen species (ROS), activates the PI3K/AKT/eNOS signaling pathway, increases the expression of neurotrophic factors (NGF, BDNF, and NT3), and ultimately improves the erectile function of diabetic mice. Our findings not only provide new conclusive evidence that the human Tie2 agonist antibody MT-100 may be a promising therapeutic strategy for the treatment of diabetic ED but also create substantial clinical applications for other complications associated with diabetes. Overall design: Control (normal mice) (n=4), DM+NC (diabetic mice+negative control) (n=4) and DM+MT-100 (diabetic mice+MT-100) (n=4)