Saikosaponin-d Alleviates Renal Inflammation and Cell Apoptosis in a Mouse Model of Sepsis via TCF7/FOSL1/Matrix Metalloproteinase 9 Inhibition

Yao, Tao; Zhang, Lei; Fu, Ye; Yao, Lina; Zhou, Cheng-Jie; Chen, Guozhong

doi:10.1128/mcb.00332-21

Cited by 22 publications

(14 citation statements)

References 24 publications

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“…Transcription factor 7 (TCF7, also known as TCF1) is one of the members of the TCF/LEF transcription factor family and participates in the transcriptional regulation of Wnt/β-catenin signal [ 1 , 3 ]. Emerging evidence has shown that TCF7 is involved in tumorigenesis and development [ 2 , 35 , 44 ], sepsis-induced renal injury [ 39 ], heart development [ 40 ], and cardiac hypertrophy [ 26 ]. However, the roles and underlying mechanism of TCF7 in HLF have not been clarified.…”

Section: Introductionmentioning

confidence: 99%

TCF7/SNAI2/miR-4306 feedback loop promotes hypertrophy of ligamentum flavum

Duan

Qiu

et al. 2022

J Transl Med

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Background Hypertrophy of ligamentum flavum (HLF) is the mainly cause of lumbar spinal stenosis (LSS), but the precise mechanism of HLF formation has not been fully elucidated. Emerging evidence indicates that transcription factor 7 (TCF7) is the key downstream functional molecule of Wnt/β-catenin signaling, which participated in regulating multiple biological processes. However, the role and underlying mechanism of TCF7 in HLF is still unclear. Methods We used mRNAs sequencing analysis of human LF and subsequent confirmation with RT-qPCR, western blot and immunohistochemistry to identified the TCF7 in HLF tissues and cells. Then effect of TCF7 on HLF progression was investigated both in vitro and in vivo. Mechanically, chromatin immunoprecipitation, dual-luciferase reporter assays, and rescue experiments were used to validate the regulation of TCF7/SNAI2/miR-4306 feedback loop. Results Our results identified for first time that the TCF7 expression was obviously elevated in HLF tissues and cells compared with control, and also found that TCF7 expression had significant positive correlation with LF thickness and fibrosis score. Notably, TCF7 inhibition suppressed the hyper-proliferation and fibrosis phenotype of HLF cells in vitro and ameliorated progression of HLF in mice in vivo, whereas TCF7 overexpression promoted hyper-proliferation and fibrosis phenotype of HLF cells in vitro. Our data further revealed that TCF7 interacted with SNAI2 promoter to transactivated the SNAI2 expression, thereby promoting hyper-proliferation and fibrosis phenotype of HLF cells in vitro. Furthermore, miR-4036 negatively regulated by SNAI2 could negatively feedback regulate TCF7 expression by directly binding to TCF7 mRNA 3’-UTR, thus inhibiting the hyper-proliferation and fibrosis phenotype of HLF cells in vitro. Conclusions Our study demonstrated that TCF7 inhibition could suppress HLF formation by modulating TCF7/SNAI2/miR-4306 feedback loop, which might be considered as a novel potential therapeutic target for HLF.

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Section: Introductionmentioning

confidence: 99%

TCF7/SNAI2/miR-4306 feedback loop promotes hypertrophy of ligamentum flavum

Duan

Qiu

et al. 2022

J Transl Med

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“…FOSL1 serves as the dominant activating protein 1 family member, can promote tumorigenesis in CRC through the FBXL2/Wnt/β-catenin axis [ 52 ]. Furthermore, FOSL1 can regulate inflammation through TCF7/FOL1/MMP9 axis [ 53 ]. Therefore, the main functions of these five core genes are antioxidant stress, anti-inflammatory and detoxification.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology-based analysis of heat clearing and detoxifying drug JC724 on the treatment of colorectal cancer

Tang¹,

Yang²,

Lü³

et al. 2023

World J Gastrointest Oncol

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BACKGROUND Heat-clearing and detoxifying drugs has protective effect on colorectal cancer (CRC). Given the complicated features of Traditional Chinese medicine formulas, network pharmacology is an effective approach for studying the multiple interactions between drugs and diseases. AIM To systematically explore the anticancer mechanism of heat-clearing and detoxifying drug JC724. METHODS This study obtained the active compounds and their targets in JC724 from Traditional Chinese Medicine System Pharmacology Database. In addition, the CRC targets were obtained from Drugbank, TTD, DisGeNET and GeneCards databases. We performed transcriptome analysis of differentially expressed genes in CRC treated with JC724. Venn diagram was used to screen the JC724-CRC intersection targets as candidate targets. Core targets were selected by protein-protein interaction network and herb ingredient-target-disease network analysis. The functional and pathway of core targets were analysed by enrichment analysis. RESULTS We found 174 active ingredients and 283 compound targets from JC724. 940 CRC-related targets were reserved from the four databases and 304 CRC differentially expressed genes were obtained by transcriptome analysis. We constructed the network and found that the five core ingredients were quercetin, β Beta sitosterol, wogonin, kaempferol and baicalein. The core JC724-CRC targets were CYP1A1 , HMOX1 , CXCL8 , NQO1 and FOSL1 . JC724 acts on multiple signaling pathways associated with CRC, including the Nrf2 signaling pathway, oxidative stress, and the IL-17 signaling pathway. CONCLUSION In this study, we systematically analyzed the active ingredients, core targets and main mechanisms of JC724 in the treatment of CRC. This study could bring a new perspective to the heat-clearing and detoxifying therapy of CRC.

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“…Fra-1 affects the differentiation and activation of immune cells, especially macrophages, as well as the secretion of many cytokines ( 17 , 121 , 133 , 138 , 142 , 198 , 199 ), but the specific mechanism remains to be further explored. The regulation of the immune response of Fra-1 makes its intracellular expression affect the outcome of many diseases, such as sepsis ( 149 ), atherosclerosis ( 155 ), myocardial infarction ( 101 ), psoriasis ( 134 ), colitis ( 162 ), etc. This evidence points at the importance of Fra-1 in immune regulation.…”

Section: Discussionmentioning

confidence: 99%

“…Down-regulation of MMP9 can reduce inflammation, while Fra-1 can occupy the promoter of MMP9 ( 170 , 171 ). The silencing of Fra-1 destroys the expression of MMP9 ( 172 ), thereby reducing sepsis-induced renal inflammation and apoptosis ( 149 ). In addition, many studies have found that sepsis in mice overexpressing Fra-1 increases the severity of lung injury ( 150 ).…”

Section: Immune-related Diseasesmentioning

confidence: 99%

The Fra-1: Novel role in regulating extensive immune cell states and affecting inflammatory diseases

Zhou

Chen

et al. 2022

Front. Immunol.

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Fra-1(Fos-related antigen1), a member of transcription factor activator protein (AP-1), plays an important role in cell proliferation, apoptosis, differentiation, inflammation, oncogenesis and tumor metastasis. Accumulating evidence suggest that the malignancy and invasive ability of tumors can be significantly changed by directly targeting Fra-1. Besides, the effects of Fra-1 are gradually revealed in immune and inflammatory settings, such as arthritis, pneumonia, psoriasis and cardiovascular disease. These regulatory mechanisms that orchestrate immune and non-immune cells underlie Fra-1 as a potential therapeutic target for a variety of human diseases. In this review, we focus on the current knowledge of Fra-1 in immune system, highlighting its unique importance in regulating tissue homeostasis. In addition, we also discuss the possible critical intervention strategy in diseases, which also outline future research and development avenues.

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Saikosaponin-d Alleviates Renal Inflammation and Cell Apoptosis in a Mouse Model of Sepsis via TCF7/FOSL1/Matrix Metalloproteinase 9 Inhibition

Cited by 22 publications

References 24 publications

TCF7/SNAI2/miR-4306 feedback loop promotes hypertrophy of ligamentum flavum

TCF7/SNAI2/miR-4306 feedback loop promotes hypertrophy of ligamentum flavum

Network pharmacology-based analysis of heat clearing and detoxifying drug JC724 on the treatment of colorectal cancer

The Fra-1: Novel role in regulating extensive immune cell states and affecting inflammatory diseases

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