Synoviolin is a novel pathogenic factor of arthropathy, chronic inflammation and metabolic disorders

2 Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan, 3INSTITUTE of Medical Science, 3 Department of Future Medical Science, Institute of Medical Science, 4 Physician, Student and Researcher Support Center Tokyo Medical University, 4INSTITUTE of Medical Science Tokyo Medical University

Материал и методы:

Inflammation is classical pathogenic concept but still very crucial for understanding many disorders even in 21st century. The purpose of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and to initiate tissue repair.

Результаты:

By contrast, chronic inflammation is recently thought to lead to a host of intractable diseases, including rheumatoid arthritis (RA), atherosclerosis, cancer, diabetes mellitus, and obesity. We recently cloned Synoviolin, an E3 ubiquitin ligase, as an overexpressing molecule in rheumatoid synovium, and has been verifying its critical roles in RA, inflammatory cytokine-signaling and fibrosis. Moreover, synoviolin deficient mice exhibited severe lean and its protected against obesity and diabetes mellitus caused by abnormalities of leptin signaling.

Заключение:

We successfully discovered Synoviolin inhibitors, LS-101 and LS-102. These drugs have inhibitory effects to Synoviolin in vitro and in vivo. We are now proceeding with the optimization of small compounds, and we hope our research will lead to the development of a new therapy for RA and fibrosis and other Synoviolin related diseases.

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