TGF-β1 induces epithelial-to-mesenchymal transition in chronic rhinosinusitis with nasal polyps through microRNA-182

Background Epithelial-to-Mesenchymal Transition (EMT) is considered as a crucial event in disease development and dysregulation of microRNAs (miRNAs) is involved in the regulation of EMT in various human diseases. Emerging evidences congregated over the years have demonstrated that miR-30a-5p was decreased in diseases and its overexpression inhibited the process of diseases via attenuating EMT. Although aberrant expression of miRNAs and occurrence of EMT were previously reported in Nasal Polyps (NPs), the role of miR-30a-5p in EMT of NPs is still remains unclear. Objective The purpose of our present study was to explore the expression and potential function of miR-30a-5p in EMT of NPs. Methods The expression of miR-30a-5p and mRNA expression level were detected by quantitative real-time PCR (qRT-PCR) in transforming growth factor β1 (TGF-β1) - induced EMT model and NPs patients. Western Blot (WB) and immunohistochemistry (IHC) were performed to evaluate the protein expression level of EMT markers. The cells mobility was assessed by Wound-Healing assay. Luciferase reporter assay was utilized to verify the relationship between Cyclin-dependent kinase 6 (CDK6) and miR-30a-5p. Results Firstly, we observed that miR-30a-5p was down-regulated notably, accompanying with the alteration of EMT markers expression in NPs tissues and EMT model induced by TGF-β1 in primary Human Nasal Epithelial Cells (pHNECs) and A549 cells in vitro. Moreover, the functional assays demonstrated that overexpression of miR-30a-5p significantly inhibited EMT and cells mobility. Subsequently, CDK6 was validated as a direct target of miR-30a-5p. Finally, we performed the rescue experiments indicating that overexpression of CDK6 eliminated the suppressive effects of miR-30a-5p in TGF-β1-induced EMT in pHNECs and A549 cells. Conclusion Taken together, our results suggested that EMT was involved in NPs, and overexpression of miR-30a-5p could attenuate EMT via repressing the expression of the CDK6 in pHNECs and A549 cells.

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Vimentin Expression in Nasal Mucosa of Patients with Exacerbated Chronic Rhinosinusitis Without Nasal Polyps

Acta Medica Bulgarica ◽

10.2478/amb-2019-0007 ◽

2019 ◽

Vol 46 (1) ◽

pp. 39-42

Author(s):

A. I. Onishchenko ◽

A. S. Tkachenko ◽

I. M. Kalashnyk ◽

V. L. Tkachenko ◽

O. A. Nakonechna ◽

...

Keyword(s):

Blood Serum ◽

Chronic Rhinosinusitis ◽

Nasal Mucosa ◽

Nasal Polyps ◽

Epithelial To Mesenchymal Transition ◽

Serum Levels ◽

Immunohistochemical Method ◽

Control Group ◽

Vimentin Expression ◽

Mesenchymal Transition

Abstract Objective. The aim of the study was to evaluate vimentin expression in inflamed nasal mucosa of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and serum levels of matrix metalloproteinase-9 (MMP-9). Material and Methods. We measured concentrations of MMP-9 in blood serum of twenty patients with CRSsNP using ELISA and compared them with the control group composed of twenty healthy subjects. Vimentin expression in nasal mucosa was studied by an immunohistochemical method. Results. Blood serum levels of MMP-9 were found to be elevated in patients with CRSsNP. The disease was also associated with the upregulation of vimentin expression both in the lamina propria and nasal epithelial layer. Conclusion. CRSsNP is accompanied by a higher number of vimentin-expressing cells in the nasal epithelium, which may indicate their epithelial-to-mesenchymal transition (EMT). We speculate that MMP-9 may contribute to the increased rate of EMT of nasal epithelial cells in CRSsNP.

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CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-β1 and IL-8

International Archives of Otorhinolaryngology ◽

10.1055/s-0041-1726043 ◽

2021 ◽

Author(s):

Wagner Vargas Souza Lino ◽

André Luis Lacerda Bachi ◽

José Arruda Mendes Neto ◽

Gabriel Caetani ◽

Jônatas Bussador do Amaral ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Nasal Polyposis ◽

Transforming Growth Factor ◽

Middle Turbinate ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Histologic Analysis ◽

Aspirin Intolerance ◽

Tgf Β1

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

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Epicatechin-3-gallate reverses TGF-β1-induced epithelial-to-mesenchymal transition and inhibits cell invasion and protease activities in human lung cancer cells

Food and Chemical Toxicology ◽

10.1016/j.fct.2016.05.009 ◽

2016 ◽

Vol 94 ◽

pp. 1-10 ◽

Cited By ~ 19

Author(s):

Shu-Fang Huang ◽

Chi-Ting Horng ◽

Yih-Shou Hsieh ◽

Yi-Hsien Hsieh ◽

Shu-Chen Chu ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Cell Invasion ◽

Epithelial To Mesenchymal Transition ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Mesenchymal Transition ◽

Human Lung Cancer Cells ◽

Tgf Β1

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Inhibition of arachidonate 15-lipoxygenase reduces the epithelial-mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps

International Forum of Allergy & Rhinology ◽

10.1002/alr.22243 ◽

2018 ◽

Vol 9 (3) ◽

pp. 270-280 ◽

Cited By ~ 7

Author(s):

Bing Yan ◽

Yang Wang ◽

Ying Li ◽

Chengshuo Wang ◽

Luo Zhang

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Eosinophilic Chronic Rhinosinusitis

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MKP2 inhibits TGF-β1-induced epithelial-to-mesenchymal transition in renal tubular epithelial cells through a JNK-dependent pathway

Clinical Science ◽

10.1042/cs20180602 ◽

2018 ◽

Vol 132 (21) ◽

pp. 2339-2355 ◽

Cited By ~ 6

Author(s):

Zhenzhen Li ◽

Xianghua Liu ◽

Fengyan Tian ◽

Ji Li ◽

Qingwei Wang ◽

...

Keyword(s):

Renal Fibrosis ◽

Epithelial To Mesenchymal Transition ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Mitogen Activated Protein Kinase ◽

Jnk Signaling ◽

Mesenchymal Transition ◽

Amino Terminal ◽

Ureter Obstruction ◽

Tgf Β1

Epithelial-to-mesenchymal transition (EMT) is a phenotypic conversion that plays a crucial role in renal fibrosis leading to chronic renal failure. Mitogen-activated protein kinase phosphatase 2 (MKP2) is a member of the dual-specificity MKPs that regulate the MAP kinase pathway involved in transforming growth factor-β1 (TGF-β1)-induced EMT. However, the function of MKP2 in the regulation of EMT and the underlying mechanisms are still largely unknown. In the present study, we detected the expression of MKP2 in an animal model of renal fibrosis and evaluated the potential role of MKP2 in tubular EMT induced by TGF-β1. We found that the expression of MKP2 was up-regulated in the tubular epithelial of unilateral ureter obstruction rats. Meanwhile, we also demonstrated that TGF-β1 up-regulated MKP2 expression in NRK-52E cells during their EMT phenotype acquisition. Importantly, overexpression of MKP2 inhibited c-Jun amino terminal kinase (JNK) signaling and partially reversed EMT induced by TGF-β1. Moreover, reducing MKP2 expression enhanced JNK phosphorylation, promoted the E-cadherin suppression and induced α-SMA expression and fibronectin secretion in response to TGF-β1, which could be rescued by a JNK inhibitor. These results provide the first evidence that MKP2 is a negative feedback molecule induced by TGF-β1, and MKP2 overexpression inhibits TGF-β1-induced EMT through the JNK signaling pathway. MKP2 could be a promising target to be used in gene therapy for renal fibrosis.

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