uPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis

Abstract Background: The present study explored the possible functions and the underlying mechanism of long Non-coding RNA LINC02085 in rheumatoid arthritis (RA). Methods: Primary fibroblast-like synoviocytes (FLS) were separated from synovial tissues and was established cell lines, then cultured for subsequent cell experiments by transfecting different vectors. Rat with AA were injected with sh-LINC02085. The progression of AA was explored by measuring arthritis score and histologic analysis. ELISA analysis was employed to detect the levels of inflammatory cytokines. CCK8 assay, migration and invasion assays were used to evaluate the proliferation, migration and invasion abilities of cells, respectively. Besides, the levels of the the PI3K/AKT pathway-related proteins were measured by WB and IF. Results: The expression level of LINC02085 was significant high in patients with RA, and positively associated with clinical indexes. We found that LINC02085 was upregulated in RA -FLS and TNF-αstimulated. And overexpression of LINC02085 could promote proliferation, migration and invasion induced by TNF-α, through upregulating the levels of TNF-αand TNFAIP2 and promoting the activation of PI3K/AKT pathway. Whereas downexpression of LINC02085 received the opposite results. Knockdown of LINC02085 significantly ameliorated the progression of AA reflected by decreased arthritis score and cartilage destruction. Conclusion: The present study revealed that LINC02085 could regulate cell growth and inflammatory response of RA-FLS by activating the PI3K/ AKT signaling pathway, subsequently playing important roles in promoting the occurrence and development of RA.

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Berberine inhibits IL-21/IL-21R mediated inflammatory proliferation of fibroblast-like synoviocytes through the attenuation of PI3K/Akt signaling pathway and ameliorates IL-21 mediated osteoclastogenesis

Cytokine ◽

10.1016/j.cyto.2018.03.005 ◽

2018 ◽

Vol 106 ◽

pp. 54-66 ◽

Cited By ~ 7

Author(s):

Palani Dinesh ◽

MahaboobKhan Rasool

Keyword(s):

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Fibroblast Like Synoviocytes

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Network Pharmacology-Based Study of Active Ingredients and Mechanisms of Compound Xuanju for Rheumatoid Arthritis

Journal of Current Medical Research and Opinion ◽

10.15520/jcmro.v3i10.336 ◽

2020 ◽

Vol 3 (10) ◽

pp. 712-723

Author(s):

Fuxue Meng ◽

Xiaomai Tao ◽

Longkuan Li ◽

Xin Yang

Keyword(s):

Rheumatoid Arthritis ◽

Signaling Pathway ◽

Akt Signaling ◽

Venn Diagram ◽

Receptor Signaling ◽

Toll Like Receptor ◽

Akt Signaling Pathway ◽

Active Ingredients ◽

Receptor Signaling Pathway ◽

Target Database

Objective: Compound Xuanju has good effects in treating rheumatoid arthritis (RA), but its composition is complex, and its active ingredients and mechanism have not been fully defined. In this study, the active ingredients and mechanism of compound Xuanju for the treatment of RA were explored through network pharmacological methods. Methods: TCMSP and TCMID, Pubmed, CNKI, Wanfang, and VIP databases were used to screen, select active pharmaceutical ingredients and targets; Drugbank disease target screening database, GeneCards database, Therapeutic The Target Database (TTD) database and DisGeNET database were used to collect RA targets, and OmicShare was used to screen compound Xuanju and RA for common targets and construct a Venn diagram. A protein target database String was used to construct a common target interaction network. OmicShare mapping software builds a "drug-active ingredient-target" network and analyzes their associations. DAVID online software performs gene annotation (GO) and KEGG pathway enrichment analysis on key targets. Results: A total of 73 effective ingredients of compound Xuanju were obtained, and corresponding to 229 targets; 2337 targets for RA. 155 key targets for potential active ingredients of compound Xuanju predicted therapeutic effect of RA, the key targets map 55 active ingredients of compound Xuanju capsules. These targets mainly involve signaling pathways such as Toll-like receptor signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway acting on RA. Conclusion: Compound Xuanju may via its potential 55 active ingredients act on 155 targets to treat RA through Toll-like receptor signaling pathway, PI3K-Akt signaling pathway, NF-κB signaling pathway, HIF-1 signaling pathway and TNF signaling pathway. This study lays the theoretical basis for the widespread application of compound Xuanju in clinical practice.

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Network pharmacology modeling identifies synergistic interaction of therapeutic and toxicological mechanisms for Tripterygium hypoglaucum Hutch

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03210-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dan Zhang ◽

Yizhu Dong ◽

Jintao Lv ◽

Bing Zhang ◽

Xiaomeng Zhang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Signaling Pathway ◽

Docking Simulation ◽

Akt Signaling ◽

Binding Activity ◽

Synergistic Interaction ◽

Network Pharmacology ◽

Akt Signaling Pathway ◽

Molecular Docking Simulation ◽

Tripterygium Hypoglaucum

Abstract Background Tripterygium hypoglaucum Hutch (THH) both has prominent efficacy and unwarranted toxicity in the treatment of autoimmune diseases. Nevertheless, its pharmacological and toxicological profiles still remain to be elucidated. In the current study, the network pharmacology approach was applied to identify synergistic interaction and mechanism of efficacy and toxicity for THH from a holistic perspective. Methods The compounds from THH were collected using literature retrieval and relevant databases. After the production of putative therapeutic targets for dominant diseases and harmful targets of adverse reactions (ADRs) induced by THH, the protein-protein interactions (PPIs), topological analysis and pathway enrichment were established to distinguish the hub targets and pathways. Additionally, the binding activity of candidate ingredients with core targets were revealed by molecular docking simulation. Results A total of eight bioactive components in THH were enrolled, and 633 targets were responsible for rheumatoid arthritis (RA), 1067 targets were corresponding to systemic lupus erythematosus (SLE), 1318 targets of ADRs were obtained. The results of enrichment analysis among THH-RA, THH-SLE and THH-ADR networks indicated that pathway in cancer, hepatitis B, rheumatoid arthritis, and PI3K-Akt signaling pathway might participate in THH for treating RA and SLE. Besides, the mechanism of ADRs that induced by THH were associated with viral carcinogenesis, p53 signaling pathway, PI3K-Akt signaling pathway, and so on. Whereas, these active ingredients of THH exerted the superior binding activities with crucial targets including STAT3, VEGFA, TP53 and MMP9 that functioned synergistically efficacy and toxicity as observed via molecular docking simulation. Conclusion The present research preliminarily interpreted the synergistic interaction of therapeutic and toxicological mechanisms for THH through the comprehensive analysis of relationship and binding activity between primary components and core targets, providing a feasible and promising approach to facilitate the development of toxic and irreplaceable herbs.

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