Nature: Key treatment for rheumatoid arthritis new targets found

Rheumatoid arthritis(Rheumatoid arthritis, or RA) is a chronic chronic disease that mainly affects the jointsIt usually causes joint fever, swelling and painThe cause of rheumatoid arthritis is unknown and is thought to be related to the body'simmunereaction and inflammatory reaction abnormalitiesExisting treatment mainly to alleviate the disease, including control of rheumatism drugs, anti-inflammatory drugs and disease drugsThe pathogenesis and effective treatment need to be further studiedIn the United States, 1.3 million adults between the ages of 30 and 60 are suffering from the diseaseRheumatoid arthritis not only damages joints, but, more seriously, increases the likelihood of heart disease, stroke, andinfectionssynovial is an interstitial tissue around the joint, consisting mainly of fibroblasts, including the inner layer (LL, layer layer) and the sub-lining layerRecent studies have shown that in rheumatoid arthritis, a portion of the lining of fibroblasts has expanded and is involved in the disease processHowever, the molecular mechanism of differentiation and expansion of these fibroblasts is not clearIn rheumatoid arthritis, fibroblasts have long been considered promising therapeutic targetsHowever, no therapeutic drugs have been developed directly targeting fibroblasts recently, the team of Soumya Raychaudhuri and Michael Brenner of Harvard Medical School published a research paper in the journal Notch Signaling drives synovialblast and synovialialblast and arthritis the researchers first determined that THE NOTCH3 signal plays a key role in the differentiation of fibroblasts around and in the interinternal layers of blood vessels expressing THY1 Using a sliding membrane fibroblast and endothelial cell co-cultured sliding membrane tissue organ (organoids) system, the researchers found that this positional characteristic is determined by endothelial cells Further data analysis of single-cell RNA sequencing (scRNA-seq) will focus on the Notch signaling pathway NOTCH3, as a Notch signaling pathway receptor for high selective expression in glioblasts, naturally became the most likely target Figure 2 While the Notch signaling pathway determines the positional characteristics of the fibroblasts , the researchers also found that NotCH3 signaling conduction contributes to the differentiation of wall cells and the expression of THY1, a step necessary for the development of inflammatory arthritis The authors used scRNA-seq to detect the expression of Notch3 in mouse slip films and determined that it was limited to wall cells and fibroblasts, consistent with increased notch receptor activation in the cells around the blood vessels, where the notch signal activity score was significantly higher than in normal conditions Figure 3 Inhibition of NOTCH3 to reduce inflammatory arthritis knocking out the Mouse Notch3 gene or using antibodies to block THE NOTCH3 signal, can significantly relieve arthritis in mice, prevent ingerify arthritis joint damage these results show that the positional properties of the fibroblasts are regulated by the Notch signal of the endothelial cell source, which is the source and pathological basis of inflammation in inflammatory arthritis , the study suggests that NOTCH3 may become a key receptor in the differentiation and pathological expansion of rheumatoid arthritis fission cells, and is expected to become a potential therapeutic target for rheumatoid arthritis Onuora S, which accompanied a review at Nat Rev Rheumatol, praised the study's main findings and the value of NOTCH3 as a potential target for RA treatments targets for rheumatoid arthritis treatment, has been a hot topic of research, in addition to the current clinical TNF alpha, IL-6, IL-17, JAK1/2/3, there are many potential new targets 2015, Nature published an article suggesting that NLRP3 could become a new target for rheumatoid arthritis treatment, see: Nature: NLRP3 May Become a New Target for Rheumatoid Arthritis Treatment 2015, Dr Bottini of the La Jolla Institute of Immunology and Allergy and the University of California, San Diego, found that the movement of fibrous sliding membrane cells is regulated by the expression of tyrosine receptor receptor salinase (RPP) Typically, RPTP is inactive in its interaction with the protein polysaccharides on the cell surface Dr Doody found that if RPTP removed from the protein polysaccharide, it would reduce the damage done to the soft tissue softening of the joints by fibrous sliding membrane cells Dr Doody added: "If we can activate RPTP, it will act as a special tool to inhibit the metastasis and invasion of sliding membrane cells in patients with rheumatoid arthritis." "The researchers synthesized a large number of small fragments of RPTP's outside the cell as molecular bait, interacting with the protein polysaccharide, occupying the RPTP-binding site, saturating it to no longer bind excess RPTP By looking at preclinical rheumatoid arthritis models, the researchers found that molecular baits can alleviate the condition See: STM: Rheumatoid arthritis treatment finds new targets
2016, scientists at the Novartis Institute for Biomedical Research (NIBR) revealed an inflammatory reaction of a molecule called "amber acid receptor GPR91" to rheumatoid arthritis and revealed the specific mechanism of the molecular signaling pathway-mediated inflammatory response The GPR91 molecule is therefore considered a potential drug target for the treatment of rheumatoid arthritis The results have been published in the journal Journal of The Eith the energy metabolism of human cells, including aerobic metabolism in aerobic environment and sugar metabolism in an oxygen-free environment, and can switch power sources according to the surrounding environment, as in hybrid vehicles Among them, sugar metabolism is closely related to inflammatory stress in inflammatory stress environment, mediated rheumatoid arthritis key inflammatory cell macrophages in switching to sugar metabolism energy, a metabolite called succinic acid is quickly transferred out of the cell, can stimulate the body's immune response, promote rheumatoid arthritis; Therefore, GPR91 inhibitors may be a promising candidate