TSG-6 Inhibits the Growth of Keloid Fibroblasts Via Mediating the TGF-β1/Smad Signaling Pathway

Weng, Xiaojuan; Tian, Xiaoyu

doi:10.1080/08941939.2020.1716894

Cited by 13 publications

(7 citation statements)

References 39 publications

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“…found that the expression level of TSG-6 within keloid lesions was significantly reduced compared to the dermis of normal skin [ 117 ], and Li et al . induced growth inhibition and G2/M phase block of keloid fibroblasts and activation of the mitochondrial apoptotic pathway by lentiviral transfection of TSG-6 in keloids [ 118 , 119 ]. Hypoxia triggers HIF-1α protein accumulation and EMT processes in keloids [ 104 , 120 ].…”

Section: Reviewmentioning

confidence: 99%

Advances in the pathogenesis and clinical application prospects of tumor biomolecules in keloid

et al. 2022

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Keloid scarring is a kind of pathological healing manifestation after skin injury and possesses various tumor properties, such as the Warburg effect, epithelial–mesenchymal transition (EMT), expression imbalances of apoptosis-related genes and the presence of stem cells. Abnormal expression of tumor signatures is critical to the initiation and operation of these effects. Although previous experimental studies have recognized the potential value of a single or several tumor biomolecules in keloids, a comprehensive evaluation system for multiple tumor signatures in keloid scarring is still lacking. This paper aims to summarize tumor biomolecules in keloids from the perspectives of liquid biopsy, genetics, proteomics and epigenetics and to investigate their mechanisms of action and feasibility from bench to bedside. Liquid biopsy is suitable for the early screening of people with keloids due to its noninvasive and accurate performance. Epigenetic biomarkers do not require changes in the gene sequence and their reversibility and tissue specificity make them ideal therapeutic targets. Nonetheless, given the ethnic specificity and genetic predisposition of keloids, more large-sample multicenter studies are indispensable for determining the prevalence of these signatures and for establishing diagnostic criteria and therapeutic efficacy estimations based on these molecules.

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Section: Reviewmentioning

confidence: 99%

Advances in the pathogenesis and clinical application prospects of tumor biomolecules in keloid

et al. 2022

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“…In addition to its representative anti-inflammatory properties, TSG-6 may modulate fibrosis by regulating the TGF-β/Smad pathway [ 31 , 33 ]. Therefore, we investigated whether TSG-6 expressed by ASCs and macrophages could regulate the fibrotic process in LX-2 cells induced by TGF-β.…”

Section: Resultsmentioning

confidence: 99%

“…As a multifunctional protein, TSG-6 can regulate the growth of fibroblasts by suppressing the TGF-β signaling pathway, leading to antifibrotic outcomes [ 31 , 32 , 33 ]. rTSG-6 significantly decreases the viability and proliferation of capsule fibroblasts by suppressing the TGF-β/Smad2 signaling pathway in frozen shoulder and enhances cellular apoptosis concurrent with a reduction in Bcl-2 expression [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

“…rTSG-6 significantly decreases the viability and proliferation of capsule fibroblasts by suppressing the TGF-β/Smad2 signaling pathway in frozen shoulder and enhances cellular apoptosis concurrent with a reduction in Bcl-2 expression [ 31 ]. TSG-6 inhibits the proliferation of keloid fibroblasts by blocking the formation of the Smad2/3/4 complex and its nuclear translocation [ 33 ]. In addition, TSG-6 contributes to liver regeneration by suppressing the activation of hepatic stellate cells in CCl 4 -treated mice, suggesting that TSG-8 may have therapeutic potential in acute liver failure [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Antifibrotic TSG-6 Expression Is Synergistically Increased in Both Cells during Coculture of Mesenchymal Stem Cells and Macrophages via the JAK/STAT Signaling Pathway

Gong

Yoon

Jung

et al. 2022

IJMS

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The pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β upregulate TNF-α-stimulated gene 6 (TSG-6); however, current knowledge about the optimal conditions for TSG-6 expression in mesenchymal stem cells (MSCs) is limited. Here, we investigated whether TSG-6 expression varies depending on the polarization state of macrophages co-cultured with adipose tissue-derived stem cells (ASCs) and analyzed the optimal conditions for TSG-6 expression in ASCs. TSG-6 expression increased in ASCs co-cultured with M0, M1, and M2 macrophages indirectly; among them, M1 macrophages resulted in the highest increase in TSG-6 expression in ASCs. TSG-6 expression in ASCs dramatically increased by combination (but not single) treatment of TNF-α, IL-1β, interferon-gamma (IFN-γ), and lipopolysaccharide (LPS). In addition, phosphorylation of signal transducer and activator of transcription (STAT) 1/3 was observed in response to IFN-γ and LPS treatment but not TNF-α and/or IL-1β. STAT1/3 activation synergistically increased TNF-α/IL-1β-dependent TSG-6 expression, and JAK inhibitors suppressed TSG-6 expression both in ASCs and macrophages. In LX-2 hepatic stellate cells, TSG-6 inhibited TGF-β-induced Smad3 phosphorylation, resulting in decreased α-smooth muscle actin (SMA) expression. Moreover, fibrotic activities of LX-2 cells induced by TGF-β were dramatically decreased after indirect co-culture with ASCs and M1 macrophages. These results suggest that a comprehensive inflammatory microenvironment may play an important role in determining the therapeutic properties of ASCs by increasing TSG-6 expression through STAT1/3 activation.

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“…Tumor necrosis factor-stimulated gene-6 (TSG-6) was shown to suppress fibrosis in keloid tissue by reducing keloid fibroblast proliferation and enhancing its apoptosis through TGF-B1 /Smad signaling pathway interference [ 58 ]. This anti-fibrosis effect was more clearly shown to suppress capsular fibroblast proliferation and accelerate its apoptosis through decreasing the expression of Bcl-2, COL1A1, TNF-α, IL-6, IL-1β, TGF-β1, and phosphorylated Smad2, and increasing BAX expression [ 21 ].…”

Section: Reviewmentioning

confidence: 99%

Cytokines' Role in the Pathogenesis and Their Targeting for the Prevention of Frozen Shoulder: A Narrative Review

Al‐Ghamdi¹,

Alyami²,

Althaqafi³

et al. 2023

Cureus

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Frozen shoulder (FS) is a common name for shoulder movement limitation with different degrees of shoulder rigidity and pain. It is characterized by varying developmental courses, different levels of shoulder movement limitation, and background ambiguity due to the multiplicity of its causative factors. Systemic inflammatory cytokines monitoring and restraining is easy to apply, fast to conduct, and needs lower costs compared to invasive methods for frozen shoulder stage evaluation and early controlling of its progress to the stage that necessitates surgical intervention. The aim of this review was to assess the recent findings concerning the role of cytokines in FS pathogenesis and the possibility of preventing or controlling their progress through targeting these cytokines by the new drugs candidates, such as hyaluronan (HA), botulinum toxin type A (BoNT A), Tetrandrine, tumor necrosis factor-stimulated gene-6 (TSG-6), and cannabidiol. Searching the PubMed site, we encountered out of 1608 records, from which 16 original studies were included for the quantitative construction of this systematic review screening of the recent studies to investigate the different FS pathogenic pathways. Most of the scenarios are centered around the inflammatory and fibrotic process triggered by synovial and capsular fibroblast stimulation. This mechanism depends mainly on alarmins cytokines, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), with the stimulation of interleukin-1 α (IL-1α), interleukin-1 β (IL-1β), tumor necrosis alpha (TNF-α), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in a joint capsule. Different pathways of transforming growth factor- β (TGF-β) stimulation, resulting in overexpression of the fibrotic factors as tenascin C (TNC), fibronectin 1, collagen I (COL 1) and collagen III (COL III), and matrix metalloproteinases (MMPs) in the capsular or synovial/capsular fibroblasts. The overall investigation of these studies led us to conclude that the new drug candidates proved their efficiency in controlling the common pathogenesis of the inflammatory and fibrotic pathways of frozen shoulder and therefore represent a prospect for easy and early controlling and efficiently treating this serious disease.

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TSG-6 Inhibits the Growth of Keloid Fibroblasts Via Mediating the TGF-β1/Smad Signaling Pathway

Cited by 13 publications

References 39 publications

Advances in the pathogenesis and clinical application prospects of tumor biomolecules in keloid

Advances in the pathogenesis and clinical application prospects of tumor biomolecules in keloid

Antifibrotic TSG-6 Expression Is Synergistically Increased in Both Cells during Coculture of Mesenchymal Stem Cells and Macrophages via the JAK/STAT Signaling Pathway

Cytokines' Role in the Pathogenesis and Their Targeting for the Prevention of Frozen Shoulder: A Narrative Review

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