The miR-103a-3p/TGFBR3 axis regulates TGF-β-induced orbital fibroblast activation and fibrosis in thyroid-eye disease

Xie, Bingyu; Wang, Xiong; Zhang, Feng; Wang, Nuo; Luo, Yunbo; Chen, Yizhi; Cao, Jun; Chen, Zhuo-Kun; Ma, Chen; Chen, Haiyan

doi:10.1016/j.mce.2022.111780

Cited by 9 publications

(1 citation statement)

References 47 publications

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“…The TGF-β receptor is a heterodimeric receptor complex composed of TGF-β type I and type II receptors [23]. It can phosphorylate Smad2 and Smad3 transcription factors and make them transfer the signal to the nucleus [35][36][37]. In this paper, we found that sST2 stimulation led to MCF activation and signi cantly increased expression of TGF-β1, P-smad2, and P-smad3.…”

Section: Discussionmentioning

confidence: 74%

sST2: A bridge between Sirt1/p53/p21 signal-induced senescence and TGF-β1/Smad2/3 regulation of cardiac fibrosis in mice viral myocarditis

Tan

Wei²,

2022

Preprint

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Soluble interleukin 1 receptor-like 1 (sST2) is a novel predictor of poor outcomes, which is involved in inflammatory response and fibrosis of myocarditis. Cardiac fibrosis is a major cause of cardiovascular disease. Cellular senescence is a state of irreversible cell cycle arrest and studies have shown that senescence of myofibroblasts can limit or reduce myocardial fibrosis. Previous studies show that cellular senescence is associated with the progress of myocarditis, and cardiac fibroblasts is closely related to cardiac fibrosis. Therefore, we investigated the role of sST2 on senescence and fibrosis in mice cardiac fibroblasts (MCF). Meanwhile, its pathological role in mice viral myocarditis (VMC) was also investigated. In vitro experiments revealed that sST2 is beneficial to activate MCF by TGF-β1/Smad2/3 signaling and inhibit cell senescence by Sirt1/P53/P21 signaling pathway. CVB3-infected mice exhibited an increased deposition of collagen in the heart and decreased MCF senescence compared to WT mice while these pathological effects are reversed by anti-ST2 mAb. In addition, we found that inhibiting the senescence of MCF is beneficial to cardiac fibrosis and this effect is achieved by paracrine action. The present study reveals a new pathogenic pathway, sST2, which leads to cardiac fibrosis of VMC by inhibiting MCF senescence.

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Section: Discussionmentioning

confidence: 74%

sST2: A bridge between Sirt1/p53/p21 signal-induced senescence and TGF-β1/Smad2/3 regulation of cardiac fibrosis in mice viral myocarditis

Tan

Wei²,

2022

Preprint

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sST2: A Bridge Between Sirt1/p53/p21 Signal-Induced Senescence and TGF-β1/Smad2/3 Regulation of Cardiac Fibrosis in Mouse Viral Myocarditis

Tan

Wei

2023

Inflammation

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Soluble interleukin 1 receptor-like 1 (sST2) is a novel predictor of poor outcomes, which is involved in inflammatory response and fibrosis of myocarditis. Cellular senescence is a state of irreversible cell cycle arrest. Studies have shown that senescence of myofibroblasts can limit or reduce cardiac fibrosis. However, the molecular mechanism of sST2 regulating cellular senescence is still unclear. Here, we investigate the role of sST2 on cellular senescence in cardiac fibrosis. Our results found that sST2 was upregulated in coxsackievirus group B type 3 (CVB3)-induced viral myocarditis (VMC), which correlated with the expression of senescence markers. In vitro, sST2 activated TGFβ signaling through the phosphorylation of the SMAD complex to induce mouse cardiac fibroblast (MCF) activation and inhibit cellular senescence by the Sirt1/p53/p21 signaling pathway. In vivo, anti-ST2 mAb attenuated CVB3-induced cardiac fibrosis. Our findings elucidate a crucial mechanism underlying through which sST2 inhibits cellular senescence and regulates MCF activation, providing a potential treatment strategy for cardiac fibrosis.

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Recent advances in TGF-β signaling pathway in COVID-19 pathogenesis: A review

Majidpour,

Azizi,

Davodabadi

et al. 2025

Microbial Pathogenesis

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The miR-103a-3p/TGFBR3 axis regulates TGF-β-induced orbital fibroblast activation and fibrosis in thyroid-eye disease

Cited by 9 publications

References 47 publications

sST2: A bridge between Sirt1/p53/p21 signal-induced senescence and TGF-β1/Smad2/3 regulation of cardiac fibrosis in mice viral myocarditis

sST2: A bridge between Sirt1/p53/p21 signal-induced senescence and TGF-β1/Smad2/3 regulation of cardiac fibrosis in mice viral myocarditis

sST2: A Bridge Between Sirt1/p53/p21 Signal-Induced Senescence and TGF-β1/Smad2/3 Regulation of Cardiac Fibrosis in Mouse Viral Myocarditis

Recent advances in TGF-β signaling pathway in COVID-19 pathogenesis: A review

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