Epithelial-Mesenchymal Transition in Atopy: A Mini-Review

Anderson, Erik D.; Alishahedani, Mohammadali E.; Myles, Ian A.

doi:10.3389/falgy.2020.628381

Cited by 4 publications

(3 citation statements)

References 135 publications

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“…This suggests alterations in the cell-cell adhesions, similar to other epithelia under inflammatory conditions [56,97]. The decreased expression of E-cadherin and the upregulation of another type of cadherin, P-cadherin, have been reported in psoriatic skin and dermatitis [98][99][100][101][102]. Changes in the cadherin function affect AJ integrity, the recruitment and activity of adaptor proteins, and therefore, the AJ-mediated mechanosignaling.…”

Section: Epidermal Cell-cell Adhesionsmentioning

confidence: 69%

Mechanotransduction in Skin Inflammation

Shutova

Boehncke

2022

Cells

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In the process of mechanotransduction, the cells in the body perceive and interpret mechanical stimuli to maintain tissue homeostasis and respond to the environmental changes. Increasing evidence points towards dysregulated mechanotransduction as a pathologically relevant factor in human diseases, including inflammatory conditions. Skin is the organ that constantly undergoes considerable mechanical stresses, and the ability of mechanical factors to provoke inflammatory processes in the skin has long been known, with the Koebner phenomenon being an example. However, the molecular mechanisms and key factors linking mechanotransduction and cutaneous inflammation remain understudied. In this review, we outline the key players in the tissue’s mechanical homeostasis, the available data, and the gaps in our current understanding of their aberrant regulation in chronic cutaneous inflammation. We mainly focus on psoriasis as one of the most studied skin inflammatory diseases; we also discuss mechanotransduction in the context of skin fibrosis as a result of chronic inflammation. Even though the role of mechanotransduction in inflammation of the simple epithelia of internal organs is being actively studied, we conclude that the mechanoregulation in the stratified epidermis of the skin requires more attention in future translational research.

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Section: Epidermal Cell-cell Adhesionsmentioning

confidence: 69%

Mechanotransduction in Skin Inflammation

Shutova

Boehncke

2022

Cells

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“…S13D-F). Comparing the variant list with the RNAseq results indicated that genes which contained DNA variants and differentially expressed transcripts were led by the known modulator of NADPH metabolism FMO2 32 and PAX6 , which may mediate AD-relevant pathways in epithelial-to-mesenchymal transition 33,34 (Fig. S13G-I).…”

Section: Resultsmentioning

confidence: 99%

Topical Steroid Withdrawal is a Targetable Excess of Mitochondrial NAD+

Shobnam,

Saksena,

Ratley

et al. 2024

Preprint

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Background: Topical glucocorticoids (more commonly termed topical corticosteroids; TCS) are first-line therapies for management of numerous skin conditions. Topical Steroid Withdrawal (TSW) is a controversial diagnosis advocated by patients with prolonged TCS exposure who report severe systemic reactions upon treatment cessation. Although the disease may be confused for eczematous disorders or dismissed outright, there have been no systematic clinical or mechanistic studies to either refute or support TSW as molecularly distinct from other dermatopathies. This study aimed to clinically differentiate TSW symptomatology, delineate abnormal molecular pathways, and investigate potential therapeutic agents. Methods: A re-analysis of a previous survey encompassing 1,889 patients with eczematous skin disease who either did or did not self-report TSW was performed to evaluate potential TSW distinguishing symptoms. We subsequently conducted a pilot study of 16 patients fitting the proposed diagnostic criteria. We then performed: tissue metabolomics, transcriptomics, and immunostaining on skin biopsies; serum metabolomics and cytokine assessments; shotgun metagenomics on microbiome skin swabs; genome sequencing; followed by functional, mechanistic studies using human skin cell lines and mice. Results: Clinically distinct TSW symptoms included burning, flushing, and thermodysregulation. Metabolomic and transcriptomic assessments both implicated elevated NAD+ oxidation stemming from increased expression of mitochondrial complex I and conversion of tryptophan into kynurenine metabolites. These abnormalities were induced by glucocorticoid exposure both in vitro and in a cohort of healthy controls (N=19) exposed to TCS. Targeting complex I via either metformin or the herbal compound berberine improved outcomes in both cell culture and in an open-label case series for patients with TSW. Conclusion: Taken together, our results suggest that TSW has a distinct dermatopathology. While future studies are needed to validate these results in larger cohorts, this work provides the first mechanistic evaluation into TSW pathology, and offers insights into clinical identification, pharmacogenomic candidates, and directed therapeutic strategies.

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“…14,15 As a result, epithelial markers such as E-cadherin are decreased, whereas mesenchymal markers including vimentin and fibroblast-specific protein 1 (FSP1) are increased, contributing to airway remodeling. 16,17 Inhibition of the EMT ameliorates ovalbumin-induced airway remodeling in mice. 18 Recent evidence has shown that the EMT reduces the expression of anti-inflammatory genes induced by glucocorticoids in human lung epithelial cells, causing steroid insensitivity, and is related to refractory asthma.…”

Section: Introductionmentioning

confidence: 99%

TSLP Induces Epithelial–Mesenchymal Transition in Nasal Epithelial Cells From Allergic Rhinitis Patients Through TGF-β1/Smad2/3 Signaling

Wang

Qian

et al. 2023

Am J Rhinol�Allergy

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Background Airway remodeling is demonstrated in Asian patients with allergic rhinitis (AR). The epithelial–mesenchymal transition (EMT) is one of the key mechanisms underlying airway remodeling. Thymic stromal lymphopoietin (TSLP) is an important contributor to airway remodeling. Although increased TSLP is found in AR, little is known about whether TSLP is involved in airway remodeling through induction of the EMT. Objective We investigated the effect of TSLP on the EMT in human nasal epithelial cells (HNECs) from AR patients. Methods Human nasal epithelial cells from AR patients were stimulated with TSLP in the absence or presence of the preincubation with a selective inhibitor of transforming growth factor beta 1 (TGF-β1) receptor (SB431542). The expression of TGF-β1 in the cells was evaluated by using real-time polymerase chain reaction, Western blotting, and immunocytochemistry. Western blotting and immunocytochemistry were used to assay EMT markers including vimentin, fibroblast-specific protein 1 (FSP1) and E-cadherin, small mothers against decapentaplegic homolog2/3 (Smad2/3), and phosphorylated Smad2/3 in the cells. The levels of extracellular matrix components such as collagens I and III in supernatants were measured by enzyme-linked immunoassay. Morphological changes of the cells were observed under inverted phase-contrast microscope. Results A concentration-dependent increase of TGF-β1 mRNA and protein was observed following stimulation with TSLP. Furthermore, TSLP decreased the expression of E-cadherin protein, but upregulated the production of FSP1 and vimentin proteins along with increased levels of collagens I and III, and the morphology of the cells was transformed into fibroblast-like shape. Additionally, a significant increase was found in phosphorylation of Smad2/3 protein. However, these effects were reversed by SB431542 preincubation. Conclusion TSLP–induced HNECs to undergo the EMT process via TGF-β1-mediated Smad2/3 activation. TSLP is an activator of the EMT in HNECs and might be a potential target for inhibiting EMT and reducing airway remodeling in AR.

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Epithelial-Mesenchymal Transition in Atopy: A Mini-Review

Cited by 4 publications

References 135 publications

Mechanotransduction in Skin Inflammation

Mechanotransduction in Skin Inflammation

Topical Steroid Withdrawal is a Targetable Excess of Mitochondrial NAD+

TSLP Induces Epithelial–Mesenchymal Transition in Nasal Epithelial Cells From Allergic Rhinitis Patients Through TGF-β1/Smad2/3 Signaling

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