TNF‑α increases inflammatory factor expression in synovial fibroblasts through the toll‑like receptor‑3‑mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis

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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TNF-α Mediates the Intrinsic and Extrinsic Pathway in Propofol-Induced Neuronal Apoptosis Via PI3K/Akt Signaling Pathway in Rat Prefrontal Cortical Neurons

Neurotoxicity Research ◽

10.1007/s12640-017-9751-8 ◽

2017 ◽

Vol 32 (3) ◽

pp. 409-419 ◽

Cited By ~ 9

Author(s):

Xiaoyuan Deng ◽

Bo Chen ◽

Bin Wang ◽

Junfang Zhang ◽

Hongliang Liu

Keyword(s):

Signaling Pathway ◽

Cortical Neurons ◽

Neuronal Apoptosis ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Extrinsic Pathway ◽

Prefrontal Cortical ◽

Tnf Α

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Regulation of Vascular Endothelial Growth Factor Expression by EMMPRIN via the PI3K-Akt Signaling Pathway

Molecular Cancer Research ◽

10.1158/1541-7786.mcr-06-0042 ◽

2006 ◽

Vol 4 (6) ◽

pp. 371-377 ◽

Cited By ~ 79

Author(s):

Yi Tang ◽

Marian T. Nakada ◽

Patricia Rafferty ◽

Jenny Laraio ◽

Francis L. McCabe ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Signaling Pathway ◽

Akt Signaling ◽

Vascular Endothelial ◽

Akt Signaling Pathway ◽

Factor Expression ◽

Growth Factor Expression ◽

Endothelial Growth Factor

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Activation of eNOS in PHT gastric mucosa is mediated by TNF-α via the PI 3-kinase/akt signaling pathway

Gastroenterology ◽

10.1016/s0016-5085(08)80266-1 ◽

2001 ◽

Vol 120 (5) ◽

pp. A54

Author(s):

Hirofumi Kawanaka ◽

Michael K. Jones ◽

Dolgor Baatar ◽

Rama Pai ◽

Imre L. Szabo ◽

...

Keyword(s):

Gastric Mucosa ◽

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Tnf Α

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The inflammatory cytokine TNF-α promotes the premature senescence of rat nucleus pulposus cells via the PI3K/Akt signaling pathway

Scientific Reports ◽

10.1038/srep42938 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 37

Author(s):

Pei Li ◽

Yibo Gan ◽

Yuan Xu ◽

Lei Song ◽

Liyuan Wang ◽

...

Keyword(s):

Signaling Pathway ◽

Nucleus Pulposus ◽

Inflammatory Cytokine ◽

Akt Signaling ◽

Premature Senescence ◽

Akt Signaling Pathway ◽

Nucleus Pulposus Cells ◽

Tnf Α

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17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood–Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model

ASN NEURO ◽

10.1177/17590914211038443 ◽

2021 ◽

Vol 13 ◽

pp. 175909142110384

Author(s):

Han Xiao ◽

Jianyang Liu ◽

Jialin He ◽

Ziwei Lan ◽

Mingyang Deng ◽

...

Keyword(s):

Oxidative Stress ◽

Brain Injury ◽

Mouse Model ◽

Intracerebral Hemorrhage ◽

Signaling Pathway ◽

Brain Edema ◽

Akt Signaling ◽

Neurological Deficits ◽

Akt Signaling Pathway ◽

And Oxidative Stress

Estrogen is neuroprotective in brain injury models, and steroid receptor cofactor 3 (SRC3) mediates estrogen signaling. We aimed to investigate whether and how SRC3 is involved in the neuroprotective effects of 17ß-estradiol (E2) in a mouse model of intracerebral hemorrhage (ICH). Ovariectomized female mice were treated with E2 after autologous blood injection-induced ICH. Brain damage was assessed by neurological deficit score, brain water content, and oxidative stress levels. Blood–brain barrier (BBB) integrity was evaluated by Evan's blue extravasation and claudin-5, ZO-1, and occludin levels. SRC3 expression and PI3K/Akt signaling pathway were examined in ICH mice treated with E2. The effect of SRC3 on E2-mediated neuroprotection was determined by examining neurological outcomes in SRC3-deficient mice undergone ICH and E2 treatment. We found that E2 alleviated ICH-induced brain edema and neurological deficits, protected BBB integrity, and suppressed oxidative stress. E2 enhanced SRC3 expression and PI3K-/Akt signaling pathway. SRC3 deficiency abolished the protective effects of E2 on ICH-induced neurological deficits, brain edema, and BBB integrity. Our results suggest that E2 suppresses ICH-induced brain injury and SRC3 plays a critical role in E2-mediated neuroprotection.

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USP25 Regulates the Proliferation and Apoptosis of Ovarian Granulosa Cells in Polycystic Ovary Syndrome by Modulating the PI3K/AKT Pathway via Deubiquitinating PTEN

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.779718 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yue Gao ◽

Jiao Chen ◽

Rui Ji ◽

Jinli Ding ◽

Yan Zhang ◽

...

Keyword(s):

Mouse Model ◽

Signaling Pathway ◽

Granulosa Cells ◽

Polycystic Ovary ◽

Granular Cell ◽

Akt Signaling ◽

Pten Expression ◽

Akt Signaling Pathway ◽

Proliferation And Apoptosis ◽

Major Factors

Background: Polycystic ovarian syndrome (PCOS) is an endocrine-related disease related to abnormal folliculogenesis and is a leading cause of infertility worldwide. Inhibition of granulosa cells (GCs) proliferation and increased GCs apoptosis have been identified as the major factors in aberrant follicle maturation.Methods: USP25 and PTEN expression in GCs from women with and without PCOS was analyzed using Western blotting. A PCOS-like mouse model was constructed using USP25 knockout and wild-type mice to explore the role of USP25 in PCOS. The human granular cell line KGN was cultured for proliferation and apoptosis assays, and the effect of USP25 on PTEN was investigated after transfection with shRNA-USP25 lentivirus.Results: USP25 expression was found to be elevated in patients and mice with PCOS. With mouse model, we observed a reduction in PCOS symptoms in mice after USP25 deletion. Increased proliferation, reduced apoptosis, activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and decreased PTEN expression were found in KGN cells after USP25 knockdown. Finally, we verified that USP25 could deubiquitinate PTEN in KGN cells.Conclusions: In this study, we investigated that USP25 can regulate the PI3K/AKT signaling pathway by deubiquitinating PTEN, thus affecting the proliferation and apoptosis of GCs and contributing to the pathogenesis of PCOS.

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LINC02085 Regulates Cell Growth and Inflammatory Response in Rheumatoid Arthritis by Regulating PI3K/ AKT Signaling Pathway

10.21203/rs.3.rs-126642/v1 ◽

2020 ◽

Author(s):

Jianting Wen ◽

Jian Liu ◽

Xin Wang ◽

Jie Wang

Keyword(s):

Rheumatoid Arthritis ◽

Cell Growth ◽

Inflammatory Response ◽

Signaling Pathway ◽

Akt Signaling ◽

Akt Pathway ◽

Migration And Invasion ◽

Arthritis Score ◽

Akt Signaling Pathway ◽

Primary Fibroblast

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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