动物实验,蛋白酶HTRA1 z-bo 2020-08-31 412

　　Rheumatoid arthritis (rheumatoid arthritis, RA) is a common autoimmune disease that affects approximately 1% of people worldwide. Clinical studies have confirmed that the serine protease HTRA1 (highrequirementA1) is closely related to arthritis. However, so far, there is no report on the regulatory mechanism of HTRA1 gene expression in mammalian cells. Institute of Zoology, Chinese Academy of Sciences

　　and other institutes of transplantation biology have conducted a series of studies on the extracellular microenvironment factors that regulate HTRA1 gene expression and intracellular signaling pathways. The results of the study showed that among the many cytokines and TLR ligands screened, IFR-γ significantly inhibited the expression of HTRA1 in fibroblasts and macrophages, while the TLR4 ligand LPS significantly increased its expression. being shown. In addition, IFN-γ significantly inhibited the up-regulation of HTRA1 gene expression by LPS. Researchers used an experimental model of rheumatoid arthritis (collagen-induced arthritis, CIA) and found that LPS treatment can significantly increase the prevalence of CIA and arthritis, as well as the expression of HTRA1 and IFN-α in the joint tissues of mice. It was found that gamma treatment significantly inhibited CIA in mice. The prevalence and arthritis disease in joint tissues and the expression level of HTRA1. At the same time, it was confirmed that LPS and IFN-γ regulate the expression and development of arthritis by blocking the activity of HTRA1 and regulating the expression of HTRA1 in joint tissues. Further molecular mechanism studies have shown that LPS directly up-regulates HTRA1 gene expression by activating the NF-κB classical pathway downstream of TLR4, while IFN-γ activates the p38MAPK-STAT1 pathway to induce HTRA1 gene expression. It has been proven that it can directly suppress. In addition, in cells isolated from human RA patients, LPS and TNC (TLR4 endogenous ligand) up-regulate the expression of HTRA1 gene, and IFN-γ inhibits its expression, and its mechanism of action is consistent with that of mouse cells. I will. This study provides new evidence and ideas for worsening RA infections, and provides new clues and platforms for IFN-γ treatment of rheumatoid arthritis, macular degeneration and other HTRA1 related diseases.