&lt;p&gt;Xanthohumol Inhibits TGF-β1-Induced Cardiac Fibroblasts Activation via Mediating PTEN/Akt/mTOR Signaling Pathway&lt;/p&gt;

Jiang, Chao; Xie, Ning; Sun, Tao; Ma, Wanjun; Zhang, Bikui; Li, Wenqun

doi:10.2147/dddt.s282206

Cited by 19 publications

(5 citation statements)

References 30 publications

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“…TGF-β1 is closely related to post-MI and ventricular remodeling and is one of the most important factors promoting myocardial fibrosis 422 . To date, recombinant TGF-β1 protein is widely used to establish the fibrosis model in vitro [423][424][425] .…”

Section: Tgf-β/smads Signaling Pathway In MImentioning

confidence: 99%

Signaling pathways and targeted therapy for myocardial infarction

Zhang

Wang

et al. 2022

Sig Transduct Target Ther

350

117

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Although the treatment of myocardial infarction (MI) has improved considerably, it is still a worldwide disease with high morbidity and high mortality. Whilst there is still a long way to go for discovering ideal treatments, therapeutic strategies committed to cardioprotection and cardiac repair following cardiac ischemia are emerging. Evidence of pathological characteristics in MI illustrates cell signaling pathways that participate in the survival, proliferation, apoptosis, autophagy of cardiomyocytes, endothelial cells, fibroblasts, monocytes, and stem cells. These signaling pathways include the key players in inflammation response, e.g., NLRP3/caspase-1 and TLR4/MyD88/NF-κB; the crucial mediators in oxidative stress and apoptosis, for instance, Notch, Hippo/YAP, RhoA/ROCK, Nrf2/HO-1, and Sonic hedgehog; the controller of myocardial fibrosis such as TGF-β/SMADs and Wnt/β-catenin; and the main regulator of angiogenesis, PI3K/Akt, MAPK, JAK/STAT, Sonic hedgehog, etc. Since signaling pathways play an important role in administering the process of MI, aiming at targeting these aberrant signaling pathways and improving the pathological manifestations in MI is indispensable and promising. Hence, drug therapy, gene therapy, protein therapy, cell therapy, and exosome therapy have been emerging and are known as novel therapies. In this review, we summarize the therapeutic strategies for MI by regulating these associated pathways, which contribute to inhibiting cardiomyocytes death, attenuating inflammation, enhancing angiogenesis, etc. so as to repair and re-functionalize damaged hearts.

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Section: Tgf-β/smads Signaling Pathway In MImentioning

confidence: 99%

Signaling pathways and targeted therapy for myocardial infarction

Zhang

Wang

et al. 2022

Sig Transduct Target Ther

350

117

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“…579 inhibited TGF- β 1-induced cardiac fibroblast activation by mediating the PTEN/Akt/mTOR pathway. It inhibited the TGF- β 1-induced proliferation, differentiation, and collagen overproduction of cardiac fibroblasts by inducing the expression of PTEN and phosphorylation of Akt and mTOR (Jiang et al 2020 ). Moreover, 579 exerted a cardioprotective effect by upregulating PTEN expression and inhibiting the phosphorylation of Akt/mTOR in vivo (Sun et al 2021 ).…”

Section: Prenylated Flavonoids With Anti-inflammatory Activitymentioning

confidence: 99%

Phytochemistry and pharmacology of natural prenylated flavonoids

Wang

Luo

et al. 2023

Arch. Pharm. Res.

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Prenylated flavonoids are a special kind of flavonoid derivative possessing one or more prenyl groups in the parent nucleus of the flavonoid. The presence of the prenyl side chain enriched the structural diversity of flavonoids and increased their bioactivity and bioavailability. Prenylated flavonoids show a wide range of biological activities, such as anti-cancer, anti-inflammatory, neuroprotective, anti-diabetic, anti-obesity, cardioprotective effects, and anti-osteoclastogenic activities. In recent years, many compounds with significant activity have been discovered with the continuous excavation of the medicinal value of prenylated flavonoids, and have attracted the extensive attention of pharmacologists. This review summarizes recent progress on research into natural active prenylated flavonoids to promote new discoveries of their medicinal value. Supplementary Information The online version contains supplementary material available at 10.1007/s12272-023-01443-4.

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“…Activation of the Smad 3 pathway plays a crucial role in the development of cardiac fibrosis, representing a significant pathological change [24][25][26][27][28][29][30] . Through the initiation of Smad 3 signaling, cardiac fibroblast differentiation can drive the progression of cardiac fibrosis 31,32 . Moreover, Smad 3 involved in the regulation of extracellular matrix protein synthesis, integrin transcription, and upregulation of α-SMA [33][34][35] .…”

Section: Introductionmentioning

confidence: 99%

CLOCK Mediates Delay in Cardiac Myofibroblast Formation and Attenuates Progression of Myocardial Fibrosis through Inhibition of Smad 3 Transcriptional Activity

Zhou,

Liao,

Chen

et al. 2023

Preprint

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IntroductionMyocardial fibrosis, characterized by excessive extracellular matrix deposition, leading to adverse cardiac remodeling and impaired function. The differentiation of cardiac fibroblasts into myofibroblasts plays a pivotal role in this process. The involvement of the core clock protein CLOCK in the formation of cardiac myofibroblasts and the advancement of myocardial fibrosis is not well understood. This study aims to investigate how CLOCK modulates cardiac myofibroblast differentiation and attenuates myocardial fibrosis by inhibiting Smad3 transcriptional activity.MethodsIn vivo, adeno-associated virus 9 was utilized for overexpression or silencing of the CLOCK gene via mice intravenous injection. In vitro experiments were conducted using primary cultures of cardiac fibroblasts isolated from mouse hearts to examine the expression levels of molecular markers associated with myofibroblast differentiation, such as α-smooth muscle actin (α-SMA) and collagen I. Additionally, a Smad3 luciferase reporter gene experiment was employed to assess the transcriptional activity of Smad3 under CLOCK regulation.ResultsThe results demonstrate that CLOCK overexpression significantly reduces the expression of α-SMA and collagen I in cardiac fibroblasts, indicating a suppression of myofibroblast formation. Conversely, CLOCK knockdown enhances the expression of these fibrotic markers. Interestingly, CLOCK was found to negatively regulate the transcriptional activity of Smad3, suggesting a potential mechanism by which CLOCK exerts its inhibitory effect on cardiac fibrosis. Specifically, CLOCK interacts with Smad3, inhibiting its nuclear translocation and subsequent activation of fibro genic gene expression.ConclusionThese findings highlight the crucial role of CLOCK in the regulation of cardiac myofibroblast formation and the progression of myocardial fibrosis. CLOCK appears to exert an inhibitory effect on fibrotic signaling pathways, partially through the inhibition of Smad3 transcriptional activity. This study provides novel insights into the molecular mechanisms underlying cardiac fibrosis and emphasizes the therapeutic potential of targeting CLOCK-mediated pathways for treating myocardial fibrosis.

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<p>Xanthohumol Inhibits TGF-β1-Induced Cardiac Fibroblasts Activation via Mediating PTEN/Akt/mTOR Signaling Pathway</p>

Cited by 19 publications

References 30 publications

Signaling pathways and targeted therapy for myocardial infarction

Signaling pathways and targeted therapy for myocardial infarction

Phytochemistry and pharmacology of natural prenylated flavonoids

CLOCK Mediates Delay in Cardiac Myofibroblast Formation and Attenuates Progression of Myocardial Fibrosis through Inhibition of Smad 3 Transcriptional Activity

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