Activating transcription factor 3 (ATF3) regulates cell growth, apoptosis, invasion and collagen synthesis in keloid fibroblast through transforming growth factor beta (TGF-beta)/SMAD signaling pathway

Wang, Xue-Ming; Liu, Xiumei; Wang, Yuting; Chen, Zhen-Yu

doi:10.1080/21655979.2020.1860491

Cited by 53 publications

(38 citation statements)

References 36 publications

(40 reference statements)

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“…22 ATF3 induces the activation of TGF-β/Smad signalling pathway in keloid fibroblasts to accelerate growth and invasion, and suppress apoptosis of keloid fibroblasts. 23 Thus, these findings show that the TGFβ/Smad signalling pathway plays a crucial role in the formation of keloids. Additionally, a previous study has found that BMP4/Smad signalling pathway induces keloid myofibroblasts to differentiate into adipocytes, thereby inhibiting the formation of keloid.…”

Section: Discussionmentioning

confidence: 68%

Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte‐like cells

Dai

Lei

2021

Basic Clin Pharma Tox

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Keloid is a type of unusually raised scar. Botulinum toxin A (BTX-A) has a great application potential in keloids treatment. Here, we investigated the functional role of BTX-A in keloids. We separated keloid tissues and normal skin tissues from keloid patients and found that the expression of myofibroblast markers, α-SMA, Collagen I, and Collagen III was increased in the keloid tissues as compared with normal skin tissues. Keloid fibroblasts derived from keloid tissues were treated with TGF-β1 to induce the differentiation of fibroblasts into myofibroblasts. The keloid myofibroblasts displayed a significant up-regulation of α-SMA. BTX-A enhanced the expression of adipocyte markers, PPARγ and C/EBPα, and increased the accumulation of lipid droplets, and reduced the expression of α-SMA, Collagen I, and Collagen III in the keloid myofibroblasts. Moreover, BTX-A enhanced the expression of BMP4 and p-smad1/5/8. Noggin (BMP4 antagonist) treatment reversed BTX-A-mediated increase of PPARγ and C/EBPα expression and lipid droplets, and down-regulation of α-SMA, Collagen I, and Collagen III in primary keloid myofibroblasts. In conclusion, BTX-A promoted the transdifferentiation of primary keloid myofibroblasts into adipocyte-like cells, which may attribute to activate BMP4/Smad signalling pathway. Thus, this study provides new insights into the mechanism of BTX-A in keloid.

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Section: Discussionmentioning

confidence: 68%

Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte‐like cells

Dai

Lei

2021

Basic Clin Pharma Tox

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“…In the neuronal system, ATF3 plays a pro-survival role in ganglion cells and neurons [ 94 ]. Consistently, ATF3 protects against doxorubicin-induced apoptosis in cardiac myocytes [ 95 ] and stress-induced cell death in renal cells, β-cells [ 96 ], and keloid fibroblasts [ 97 ]. The collective evidence suggests that ATF3 plays a protective role in cell-stressed conditions.…”

Section: Discussionmentioning

confidence: 99%

Activating Transcription Factor 3 Protects against Restraint Stress-Induced Gastrointestinal Injury in Mice

Chuang

Pethaperumal

Siwakoti

et al. 2021

Cells

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Psychological stress increases the risk of gastrointestinal (GI) tract diseases, which involve bidirectional communication of the GI and nerves systems. Acute stress leads to GI ulcers; however, the mechanism of the native cellular protection pathway, which safeguards tissue integrality and maintains GI homeostasis, remains to be investigated. In a mouse model of this study, restraint stress induced GI leakage, abnormal tight junction protein expression, and cell death of gut epithelial cells. The expression of activating transcription factor 3 (ATF3), a stress-responsive transcription factor, is upregulated in the GI tissues of stressed animals. ATF3-deficient mice displayed an exacerbated phenotype of GI injuries. These results suggested that, in response to stress, ATF3 is part of the native cellular protective pathway in the GI system, which could be a molecular target for managing psychological stress-induced GI tract diseases.

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“…Li believed that ATF3 expression in cardiac fibroblast could protect against heart failure, while ATF3 knockout markedly exaggerated hypertensive ventricular remodeling ( Li et al, 2017 ). Moreover, it is reported that ATF3 could also regulate cell growth, apoptosis, invasion, and collagen synthesis in keloid fibroblast through TGF-beta/SMAD signaling pathway ( Wang et al, 2021 ). In our study, we first verified that ATF3 overexpression could promote the proliferation, migration, and invasion of RA-FLS and MH7A ( Figures 8 , 9 ) and could stimulate those cells to secrete more pro-inflammation cytokines, like IL-1β, IL-6, and IL-8 ( Figure 10 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of ATF3 Serving as a Potential Biomarker and Correlating With Pharmacotherapy Response and Immune Infiltration Characteristics in Rheumatoid Arthritis

Zhang

et al. 2021

Front. Mol. Biosci.

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Background: Although disease-modifying antirheumatic drugs (DMARDs) have significantly improved the prognosis of patients with rheumatoid arthritis (RA), approximately 40% of RA patients have limited response. Therefore, it was essential to explore new biomarkers to improve the therapeutic effects on RA. This study aimed to develop a new biomarker and validate it by an in vitro study.Methods: The RNA-seq and the clinicopathologic data of RA patients were downloaded from Gene Expression Omnibus (GEO) databases. Differentially expressed genes were screened in the GPL96 and GPL570 databases. Then, weighted gene co-expression network analysis (WGCNA) was used to explore the most correlated gene modules to normal and RA synovium in the GPL96 and GPL570 databases. After that, the differentially expressed genes were intersected with the correlated gene modules to find the potential biomarkers. The CIBERSORT tool was applied to investigate the relationship between activated transcription factor 3 (ATF3) expression and the immune cell infiltration, and Gene Set Enrichment Analysis (GSEA) was used to investigate the related signaling pathways of differentially expressed genes in the high and low ATF3 groups. Furthermore, the relationships between ATF3 expression and clinical parameters were also explored in the GEO database. Finally, the role of ATF3 was verified by in vitro cell experiments.Results: We intersected the differentially expressed genes and the most correlated gene modules in the GPL570 and GPL96 databases and identified that ATF3 is a significant potential biomarker and correlates with some clinical–pharmacological variables. Immune infiltration analysis showed that activated mast cells had a significant infiltration in the high ATF3 group in the two databases. GSEA showed that metabolism-associated pathways belonged to the high ATF3 groups and that inflammation and immunoregulation pathways were enriched in the low ATF3 group. Finally, we validated that ATF3 could promote the proliferation, migration, and invasion of RA fibroblast-like synoviocyte (FLS) and MH7A. Flow cytometry showed that ATF3 expression could decrease the proportion of apoptotic cells and increase the proportion of S and G2/M phase cells.Conclusion: We successfully identified and validated that ATF3 could serve as a novel biomarker in RA, which correlated with pharmacotherapy response and immune cell infiltration.

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Activating transcription factor 3 (ATF3) regulates cell growth, apoptosis, invasion and collagen synthesis in keloid fibroblast through transforming growth factor beta (TGF-beta)/SMAD signaling pathway

Abstract: 2021) Activating transcription factor 3 (ATF3) regulates cell growth, apoptosis, invasion and collagen synthesis in keloid fibroblast through transforming growth factor beta (TGF-beta)/SMAD signaling pathway,

Cited by 53 publications

References 36 publications

Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte‐like cells

Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte‐like cells

Activating Transcription Factor 3 Protects against Restraint Stress-Induced Gastrointestinal Injury in Mice

Identification and Validation of ATF3 Serving as a Potential Biomarker and Correlating With Pharmacotherapy Response and Immune Infiltration Characteristics in Rheumatoid Arthritis

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