A-Kinase Anchoring Proteins Diminish TGF-β1/Cigarette Smoke-Induced Epithelial-To-Mesenchymal Transition

Zuo, Haoxiao; Trombetta-Lima, Marina; Heijink, Irene H.; Veen, Christina H T J van der; Hesse, Laura; Faber, Klaas Nico; Poppinga, W. J.; Maarsingh, Harm; Nikolaev, Viacheslav O.; Schmidt, Martina

doi:10.3390/cells9020356

Cited by 17 publications

(13 citation statements)

References 45 publications

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“…Mitochondria thus appears to play a pivotal role in immune cell metabolic reprogramming ensuring, as a signaling hub, the adequate crosstalk between immunity control and cellular energy providing (137,(159)(160)(161)(162). To that end, mitochondria transfer is under investigation.…”

Section: Metabolism At the Heart Of Mscs And Immune Cells Crosstalkmentioning

confidence: 99%

MSCs and Inflammatory Cells Crosstalk in Regenerative Medicine: Concerted Actions for Optimized Resolution Driven by Energy Metabolism

2021

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Mesenchymal stromal cells (MSCs) are currently widely used in cell based therapy regarding to their remarkable efficacy in controlling the inflammatory status in patients. Despite recent progress and encouraging results, inconstant therapeutic benefits are reported suggesting that significant breakthroughs in the understanding of MSCs immunomodulatory mechanisms of action remains to be investigated and certainly apprehended from original point of view. This review will focus on the recent findings regarding MSCs close relationship with the innate immune compartment, i.e. granulocytes and myeloid cells. The review will also consider the intercellular mechanism of communication involved, such as factor secretion, cell-cell contact, extracellular vesicles, mitochondria transfer and efferocytosis. Immune-like-properties of MSCs supporting part of their therapeutic effect in the clinical setting will be discussed, as well as their potentials (immunomodulatory, anti-bacterial, anti-inflammatory, anti-oxidant defenses and metabolic adaptation…) and effects mediated, such as cell polarization, differentiation, death and survival on various immune and tissue cell targets determinant in triggering tissue regeneration. Their metabolic properties in term of sensing, reacting and producing metabolites influencing tissue inflammation will be highlighted. The review will finally open to discussion how ongoing scientific advances on MSCs could be efficiently translated to clinic in chronic and age-related inflammatory diseases and the current limits and gaps that remain to be overcome to achieving tissue regeneration and rejuvenation.

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Section: Metabolism At the Heart Of Mscs And Immune Cells Crosstalkmentioning

confidence: 99%

MSCs and Inflammatory Cells Crosstalk in Regenerative Medicine: Concerted Actions for Optimized Resolution Driven by Energy Metabolism

2021

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“…Numerous studies reveal that the Wnt/β-catenin signaling plays a crucial role in airway remodeling and EMT in COPD [7,23]. We rst validated that CSE induced activation of the Wnt/β-Catenin signaling.…”

Section: Fermt3 Regulates Cse-induced Emt Via Wnt/β-catenin Signalingmentioning

confidence: 78%

“…It is involved in airway brosis and subsequent air ow obstruction in COPD and may be a potential mechanism for the high prevalence of lung cancer in patients with COPD [6]. Recent studies con rmed that cigarette smoking-induced EMT in human type II AEC cell line (A549 ) [18], the human bronchial epithelial cell line (16-HBE cells) [19,25,26], another human bronchial epithelial cell line BEAS-2B [22,23], and primary human bronchial epithelial cell of smokers with COPD in vitro [27].In the present study, we evaluated the effect of cigarette smoke on EMT in vivo and in vitro. The results con rmed that cigarette smoke-induced EMT in CS-exposure mice.…”

Section: Discussionmentioning

confidence: 99%

FERMT3 Mediates Cigarette Smoke-induced Epithelial-mesenchymal Transition Through Wnt/β-Catenin Signaling

Chen

Lin

et al. 2021

Preprint

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Background: Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial-mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated. Methods: The present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Two GEO datasets were combined to identify FERMT3 involved in COPD. The expression of FERMT3 was identified in COPD from two GEO datasets. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT. Results: Based on the GEO dataset analysis, the expression of FERMT3 was downregulated in COPD-smoker bronchoalveolar lavage fluid than that in Non-smoker. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling. Conclusions: In summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial-mesenchymal transition through Wnt/β-Catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.

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“…EMT is a critical stage during fibrosis development in silicosis, and plays an important part in lung fibrosis. 16 , 17 , 24 , 25 EMT is the process through which epithelial cells acquire the characteristics of mesenchymal cells following activation by growth factors such as TGF-β1. 26 , 27 Growth factors trigger upregulation of genes usually expressed in mesenchymal cells (eg, α-SMA, vimentin) and downregulation of the genes expressed in epithelial cells (eg, E-cadherin, SP-A).…”

Section: Discussionmentioning

confidence: 99%

<p>Synthesis and Identification of a Novel Peptide, Ac-SDK (Biotin) Proline, That Can Elicit Anti-Fibrosis Effects in Rats Suffering from Silicosis</p>

Wang¹,

Qian²,

Gao³

et al. 2020

DDDT

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Background: N-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a short peptide with an anti-silicosis effect. However, the short biological half-life and low plasma concentration of Ac-SDKP hamper discovery of specific targets in organisms and reduce the anti-silicosis effect. A novel peptide, Ac-SDK (biotin) proline, termed "Ac-B", with anti-fibrotic properties was synthesized. Methods: Ac-B was detected quantitatively by high-performance liquid chromatography. Phagocytosis of Ac-B by the alveolar epithelial cell line A549 was investigated by confocal laser scanning microscopy and flow cytometry. To further elucidate the cellular-uptake mechanism of Ac-B, chemical inhibitors of specific uptake pathways were used. After stimulation with transforming growth factor-β1, the effects of Ac-B on expression of the myofibroblast marker vimentin and accumulation of collagen type I in A549 cells were analyzed by Western blotting. Sirius Red staining and immunohistochemical analyses of the effect of Ac-B on expression of α-smooth muscle actin (SMA) in a rat model of silicosis were undertaken. Results: Ac-B had good traceability during the uptake, entry, and distribution in cells. Ac-B treatment prevented an increase in α-SMA expression in vivo and in vitro and was superior to that of Ac-SDKP. Caveolae-mediated uptake of Ac-B by A549 cells led to achieving antiepithelial-mesenchymal transformation (EMT) effects. Conclusion: Ac-B had an anti-fibrotic effect and could be a promising agent for the fibrosis observed in silicosis in the future.

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A-Kinase Anchoring Proteins Diminish TGF-β1/Cigarette Smoke-Induced Epithelial-To-Mesenchymal Transition

Cited by 17 publications

References 45 publications

MSCs and Inflammatory Cells Crosstalk in Regenerative Medicine: Concerted Actions for Optimized Resolution Driven by Energy Metabolism

MSCs and Inflammatory Cells Crosstalk in Regenerative Medicine: Concerted Actions for Optimized Resolution Driven by Energy Metabolism

FERMT3 Mediates Cigarette Smoke-induced Epithelial-mesenchymal Transition Through Wnt/β-Catenin Signaling

<p>Synthesis and Identification of a Novel Peptide, Ac-SDK (Biotin) Proline, That Can Elicit Anti-Fibrosis Effects in Rats Suffering from Silicosis</p>

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