Non-canonical (non-SMAD2/3) TGF-β signaling in fibrosis: Mechanisms and targets

Finnson, Kenneth W.; Almadani, Yasser; Philip, Anie

doi:10.1016/j.semcdb.2019.11.013

Cited by 116 publications

(101 citation statements)

References 102 publications

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“…The mitogen-activated protein kinases (MAPKs), including JNK, have been linked to the aberrant activation of fibroblasts and subsequent fibrosis [92,101]. JNK is activated by TGFβ and PDGF in Systemic sclerosis (SSc) fibroblasts.…”

Section: Jnk Connections With Tgfβ and Pdgf In Dermal Fibrosismentioning

confidence: 99%

The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer

Hammouda

Ford

Liu

et al. 2020

Cells

171

114

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The c-Jun N-terminal kinases (JNKs), with its members JNK1, JNK2, and JNK3, is a subfamily of (MAPK) mitogen-activated protein kinases. JNK signaling regulates a wide range of cellular processes, including cell proliferation, differentiation, survival, apoptosis, and inflammation. Dysregulation of JNK pathway is associated with a wide range of immune disorders and cancer. Our objective is to provide a review of JNK proteins and their upstream regulators and downstream effector molecules in common skin disorders, including psoriasis, dermal fibrosis, scleroderma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.

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Section: Jnk Connections With Tgfβ and Pdgf In Dermal Fibrosismentioning

confidence: 99%

The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer

Hammouda

Ford

Liu

et al. 2020

Cells

171

114

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“…Taken together, targeting TGF-β signaling is promising for the treatment of fibrotic diseases. While not discussed here, several non-canonical TGF-β signaling interventions have entered clinical trials, and readers are pointed to a relevant review [8].…”

Section: Tgf-β Inhibition and Fibrotic Diseasesmentioning

confidence: 99%

“…SMAD7 is a negative feedback inhibitor of TGF-β/SMAD canonical signaling that physically compete with canonical SMAD proteins, as well as recruit E3 ubiquitin ligases to induce proteaosomal degradation of TGF-β signaling components to dampen TGF-β/SMAD signaling [6,7]. TGF-β also induces non-SMAD signaling (non-canonical pathways), including Rho GTPases (Rho), mitogen-activated protein kinases (MAPK), phosphoinositide-3-kinase (PI3K), and p53 [8,9]. These non-SMAD signaling pathways are involved in TGF-β-mediated biological responses, and they can also regulate the canonical SMAD pathway [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Transforming Growth Factor-β Signaling in Fibrotic Diseases and Cancer-Associated Fibroblasts

et al. 2020

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Transforming growth factor-β (TGF-β) signaling is essential in embryo development and maintaining normal homeostasis. Extensive evidence shows that TGF-β activation acts on several cell types, including epithelial cells, fibroblasts, and immune cells, to form a pro-fibrotic environment, ultimately leading to fibrotic diseases. TGF-β is stored in the matrix in a latent form; once activated, it promotes a fibroblast to myofibroblast transition and regulates extracellular matrix (ECM) formation and remodeling in fibrosis. TGF-β signaling can also promote cancer progression through its effects on the tumor microenvironment. In cancer, TGF-β contributes to the generation of cancer-associated fibroblasts (CAFs) that have different molecular and cellular properties from activated or fibrotic fibroblasts. CAFs promote tumor progression and chronic tumor fibrosis via TGF-β signaling. Fibrosis and CAF-mediated cancer progression share several common traits and are closely related. In this review, we consider how TGF-β promotes fibrosis and CAF-mediated cancer progression. We also discuss recent evidence suggesting TGF-β inhibition as a defense against fibrotic disorders or CAF-mediated cancer progression to highlight the potential implications of TGF-β-targeted therapies for fibrosis and cancer.

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“…The TGF-β is a dynamic and sophisticated molecular signaling pathway with pleiotropic impacts that modulate various biological mechanisms such as cell proliferation, cell differentiation, angiogenesis, motility, invasion, and immune response (Bai et al, 2019;Boguslawska et al, 2019;Finnson et al, 2019;Soleimani et al, 2019;Lai et al, 2020;Li and Wu, 2020;Lin and Wu, 2020;Tzavlaki and Moustakas, 2020). The TGF-β family possesses 33 genes that are capable of encoding homodimeric or heterodimeric secreted cytokines (Heldin and Moustakas, 2016;Derynck and Budi, 2019).…”

Section: Transforming Growth Factor-beta Signaling Pathway: From Basimentioning

confidence: 99%

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

et al. 2020

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Immune response, proliferation, migration and angiogenesis are juts a few of cellular events that are regulated by transforming growth factor-β (TGF-β) in cells. A number of studies have documented that TGF-β undergoes abnormal expression in different diseases, e.g., diabetes, cancer, fibrosis, asthma, arthritis, among others. This has led to great fascination into this signaling pathway and developing agents with modulatory impact on TGF-β. Curcumin, a natural-based compound, is obtained from rhizome and roots of turmeric plant. It has a number of pharmacological activities including antioxidant, anti-inflammatory, anti-tumor, anti-diabetes and so on. Noteworthy, it has been demonstrated that curcumin affects different molecular signaling pathways such as Wnt/β-catenin, Nrf2, AMPK, mitogen-activated protein kinase and so on. In the present review, we evaluate the potential of curcumin in regulation of TGF-β signaling pathway to corelate it with therapeutic impacts of curcumin. By modulation of TGF-β (both upregulation and down-regulation), curcumin ameliorates fibrosis, neurological disorders, liver disease, diabetes and asthma. Besides, curcumin targets TGF-β signaling pathway which is capable of suppressing proliferation of tumor cells and invading cancer cells.

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Non-canonical (non-SMAD2/3) TGF-β signaling in fibrosis: Mechanisms and targets

Cited by 116 publications

References 102 publications

The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer

The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer

Transforming Growth Factor-β Signaling in Fibrotic Diseases and Cancer-Associated Fibroblasts

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

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