| First Author | Reches G | Year | 2024 |
| Journal | Biomed Pharmacother | Volume | 175 |
| Pages | 116622 | PubMed ID | 38653114 |
| Mgi Jnum | J:349800 | Mgi Id | MGI:7658584 |
| Doi | 10.1016/j.biopha.2024.116622 | Citation | Reches G, et al. (2024) Controlling autoimmune diabetes onset by targeting Protease-Activated Receptor 2. Biomed Pharmacother 175:116622 |
| abstractText | BACKGROUND: Type 1 diabetes (T1D) is a challenging autoimmune disease, characterized by an immune system assault on insulin-producing beta-cells. As insulin facilitates glucose absorption into cells and tissues, beta-cell deficiency leads to elevated blood glucose levels on one hand and target-tissues starvation on the other. Despite efforts to halt beta-cell destruction and stimulate recovery, success has been limited. Our recent investigations identified Protease-Activated Receptor 2 (Par2) as a promising target in the battle against autoimmunity. We discovered that Par2 activation's effects depend on its initial activation site: exacerbating the disease within the immune system but fostering regeneration in affected tissue. METHODS: We utilized tissue-specific Par2 knockout mice strains with targeted Par2 mutations in beta-cells, lymphocytes, and the eye retina (as a control) in the NOD autoimmune diabetes model, examining T1D onset and beta-cell survival. RESULTS: We discovered that Par2 expression within the immune system accelerates autoimmune processes, while its presence in beta-cells offers protection against beta-cell destruction and T1D onset. This suggests a dual-strategy treatment for T1D: inhibiting Par2 in the immune system while activating it in beta-cells, offering a promising strategy for T1D. CONCLUSIONS: This study highlights Par2's potential as a drug target for autoimmune diseases, particularly T1D. Our results pave the way for precision medicine approaches in treating autoimmune conditions through targeted Par2 modulation. |
