Crosstalk between TGF-&amp;beta; signaling and epigenome

Bai, Jianbo; Xi, Qiaoran

doi:10.1093/abbs/gmx122

Cited by 33 publications

(15 citation statements)

References 98 publications

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“…In that sense, the aspects of TGF-β signaling intracellular transduction and the crosstalk with other pathways have been the subject of extensive reviews [23][24][25][26]. In the end, the ability of TGF-β stimulation to promote long-term modulation of gene expression is affected by concomitant circumstances, for instance, the epigenetic status or the microRNA profile of the targeted cell [27,28], among others. Altogether, the sum of mechanisms involved in TGF-β signaling implies countless possibilities for modulation at any level, making the final outcome highly dependent on cell type and context.…”

Section: Tgf-β Signaling: a Context Dependent Mechanismmentioning

confidence: 99%

Role of TGF-β in Skin Chronic Wounds: A Keratinocyte Perspective

Liarte

Bernabé‐García

Nicolás

2020

Cells

139

105

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Chronic wounds are characterized for their incapacity to heal within an expected time frame. Potential mechanisms driving this impairment are poorly understood and current hypotheses point to the development of an unbalanced milieu of growth factor and cytokines. Among them, TGF-β is considered to promote the broadest spectrum of effects. Although it is known to contribute to healthy skin homeostasis, the highly context-dependent nature of TGF-β signaling restricts the understanding of its roles in healing and wound chronification. Historically, low TGF-β levels have been suggested as a pattern in chronic wounds. However, a revision of the available evidence in humans indicates that this could constitute a questionable argument. Thus, in chronic wounds, divergences regarding skin tissue compartments seem to be characterized by elevated TGF-β levels only in the epidermis. Understanding how this aspect affects keratinocyte activities and their capacity to re-epithelialize might offer an opportunity to gain comprehensive knowledge of the involvement of TGF-β in chronic wounds. In this review, we compile existing evidence on the roles played by TGF-β during skin wound healing, with special emphasis on keratinocyte responses. Current limitations and future perspectives of TGF-β research in chronic wounds are discussed.

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Section: Tgf-β Signaling: a Context Dependent Mechanismmentioning

confidence: 99%

Role of TGF-β in Skin Chronic Wounds: A Keratinocyte Perspective

Liarte

Bernabé‐García

Nicolás

2020

Cells

139

105

View full text Add to dashboard Cite

show abstract

“…TGF-β can be described as a cytokine with multifunctionality, whose expression takes place by various kinds of cells (22). The superfamily of TGF-β included the TGF-β isoforms (TGF-β1, TGF-β2, and TGF-β3) and activins, as well as inhibins, growthdifferentiating factors, bone morphogenetic proteins (BMPs), together with anti-müllerian hormones (AMH) as suborders (23,24). TGF-β plays a role in different diseases such as cardiac abnormality, cardiac fibrosis, failure of the heart, and remodeling of chamber, as well as cardiac hypertrophy (22) (Figure 1).…”

Section: Tgf-β/smad Signaling In Cardiac Fibrosismentioning

confidence: 99%

Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players

Saadat

Noureddini

Mahjoubin‐Tehran

et al. 2021

Front. Cardiovasc. Med.

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Unintended cardiac fibroblast proliferation in many pathophysiological heart conditions, known as cardiac fibrosis, results in pooling of extracellular matrix (ECM) proteins in the heart muscle. Transforming growth factor β (TGF-β) as a pivotal cytokine/growth factor stimulates fibroblasts and hastens ECM production in injured tissues. The TGF-β receptor is a heterodimeric receptor complex on the plasma membrane, made up from TGF-β type I, as well as type II receptors, giving rise to Smad2 and Smad3 transcription factors phosphorylation upon canonical signaling. Phosphorylated Smad2, Smad3, and cytoplasmic Smad4 intercommunicate to transfer the signal to the nucleus, culminating in provoked gene transcription. Additionally, TGF-β receptor complex activation starts up non-canonical signaling that lead to the mitogen-stimulated protein kinase cascade activation, inducing p38, JNK1/2 (c-Jun NH2-terminal kinase 1/2), and ERK1/2 (extracellular signal–regulated kinase 1/2) signaling. TGF-β not only activates fibroblasts and stimulates them to differentiate into myofibroblasts, which produce ECM proteins, but also promotes fibroblast proliferation. Non-coding RNAs (ncRNAs) are important regulators of numerous pathways along with cellular procedures. MicroRNAs and circular long ncRNAs, combined with long ncRNAs, are capable of affecting TGF-β/Smad signaling, leading to cardiac fibrosis. More comprehensive knowledge based on these processes may bring about new diagnostic and therapeutic approaches for different cardiac disorders.

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“…Epigenetic changes can affect the TGF-β ligands or pathway components and TGF-β-related gene expression [ 245 ]. Besides, the activated SMAD in the TGF-β/BMP pathway can recruit the epigenetic regulators in nucleus such as HATs, HDACs, DNMTs and lncRNAs which affects the expression of TGF-β target genes [ 249 ]. Differentially methylated regions were observed in genes encoding proteins linked to the TGF-β signaling pathway in BCSCs compare to non‐BCSCs.…”

Section: Epigenetic Alterations Of Signaling Pathways In Csc Resistancementioning

confidence: 99%

Current understanding of epigenetics mechanism as a novel target in reducing cancer stem cells resistance

et al. 2021

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At present, after extensive studies in the field of cancer, cancer stem cells (CSCs) have been proposed as a major factor in tumor initiation, progression, metastasis, and recurrence. CSCs are a subpopulation of bulk tumors, with stem cell-like properties and tumorigenic capabilities, having the abilities of self-renewal and differentiation, thereby being able to generate heterogeneous lineages of cancer cells and lead to resistance toward anti-tumor treatments. Highly resistant to conventional chemo- and radiotherapy, CSCs have heterogeneity and can migrate to different organs and metastasize. Recent studies have demonstrated that the population of CSCs and the progression of cancer are increased by the deregulation of different epigenetic pathways having effects on gene expression patterns and key pathways connected with cell proliferation and survival. Further, epigenetic modifications (DNA methylation, histone modifications, and RNA methylations) have been revealed to be key drivers in the formation and maintenance of CSCs. Hence, identifying CSCs and targeting epigenetic pathways therein can offer new insights into the treatment of cancer. In the present review, recent studies are addressed in terms of the characteristics of CSCs, the resistance thereof, and the factors influencing the development thereof, with an emphasis on different types of epigenetic changes in genes and main signaling pathways involved therein. Finally, targeted therapy for CSCs by epigenetic drugs is referred to, which is a new approach in overcoming resistance and recurrence of cancer.

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Crosstalk between TGF-β signaling and epigenome

Cited by 33 publications

References 98 publications

Role of TGF-β in Skin Chronic Wounds: A Keratinocyte Perspective

Role of TGF-β in Skin Chronic Wounds: A Keratinocyte Perspective

Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players

Current understanding of epigenetics mechanism as a novel target in reducing cancer stem cells resistance

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