Regulation of Transforming Growth Factor-β1 Activation and Expression in the Tissue Remodeling Involved in Chronic Rhinosinusitis

Kou, Wei; Hu, Guohua; Yao, Hongbing; Wang, Xiaoqiang; Shen, Yang; Kang, Hong-Yong; Hong, Suling

doi:10.1159/000338799

Cited by 24 publications

(23 citation statements)

References 75 publications

(40 reference statements)

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“…Many previous papers in western countries have reported that patients with CRSsNP showed higher levels of TGF-β expression, whereas those with CRSwNP showed lower TGF-β expression levels compared with the control subjects [6, 14, 16, 17]. However, there was no significant difference in TGF-β between our ECRS and non-ECRS groups.…”

Section: Discussioncontrasting

confidence: 55%

IL-5 and IL-6 are increased in the frontal recess of eosinophilic chronic rhinosinusitis patients

Kubota

Takeno

Taruya

et al. 2017

J of Otolaryngol - Head & Neck Surg

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BackgroundEosinophilic chronic frontal sinusitis is difficult to treat compared with non-eosinophilic sinusitis because of recurring inflammation and polyp formation in the frontal recess after the post-operative follow-up period. Studying inflammatory mediators in the frontal recess of eosinophilic chronic rhinosinusitis (ECRS) patients and non-eosinophilic chronic rhinosinusitis (non-ECRS) patients may lead to a better understanding of the pathogenesis of chronic frontal sinusitis.MethodsHomogenates of sinonasal mucosa from 20 non-ECRS patients and 36 ECRS patients were measured for levels of transforming growth factor (TGF)-β, interleukin (IL)-5, IL-6, and inducible nitric oxide synthase (iNOS) using real-time RT-PCR and TaqMan gene expression assays. Sinonasal mucosal specimens were obtained from the frontal recess, ethmoid sinus, and nasal polyp separately.ResultsThe expression of IL-5 was significantly elevated in all sinonasal regions tested in the ECRS group, but absent in non-ECRS patients. Furthermore, the ECRS patients showed significantly increased levels of IL-5 in the frontal recess mucosa compared with ethmoid sinus mucosa. IL-6 was also significantly increased in the frontal recess mucosa compared with ethmoid sinus mucosa and nasal polyps in these patients. There were no significant differences in the levels of TGF-β or iNOS between the ECRS and non-ECRS groups in any sinonasal region tested.ConclusionsThis study is the first to characterize the cytokine milieu in the frontal recess of ECRS patients. We should keep these cytokine profiles in mind when we treat ECRS patients with frontal sinusitis.

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Section: Discussioncontrasting

confidence: 55%

IL-5 and IL-6 are increased in the frontal recess of eosinophilic chronic rhinosinusitis patients

Kubota

Takeno

Taruya

et al. 2017

J of Otolaryngol - Head & Neck Surg

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“…Typically, it has been divided into CRSwNP and CRSsNP based on the presence or absence of polyps on endoscopic examinations [1]. CRS results in a substantial burden with a prevalence of about 12.5% in the population [50] and is estimated to affect over 10 million patients in the US, leading to total annual costs of USD 22 billion [51]. Besides inflammation, these chronic upper airway disorders are characterized by remodeling of structural components, especially of the epithelium [13].…”

Section: Discussion/conclusionmentioning

confidence: 99%

TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

Zhu

et al. 2019

Int Arch Allergy Immunol

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Objectives: To characterize the epithelial-mesenchymal transition (EMT) in chronic rhinosinusitis with nasal polyps (CRSwNP) and to investigate the mechanism by which microRNA-21 (miR-21) regulates EMT in CRSwNP. Method: (1) Tissue experiments: Mucosa tissues were collected from 13 patients with CRSwNP and 12 patients with CRS without nasal polyps (CRSsNP), as well as 11 patients without CRS (controls). Protein localization and quantification were achieved by immunofluorescence staining and Western blotting, involving the epithelial marker protein E-cadherin and the mesenchymal marker proteins α-smooth muscle actin (α-SMA), fibronectin, and vimentin. Quantitative RT-PCR was used to detect the relative expression levels of miR-21 and TGF-β1 mRNAs. (2) Cellular experiments: Primary human nasal epithelial cells (PHNECs) treated with TGF-β1, or TGF-β1 with miR-21 inhibitor, or miR-21 mimics alone were observed for morphology changes under a phase-contrast microscope. The expression levels of epithelial/mesenchymal marker proteins were determined as aforementioned. PTEN and phosphorylated Akt were detected by Western blotting. Results: (1) Tissue experiments: Compared with the CRSsNP and control groups, the expression of E-cadherin was downregulated in the CRSwNP group, whereas the expression of TGF-β1, α-SMA, fibronectin, and vimentin was upregulated. The expression levels of miR-21 and TGF-β1 mRNAs in CRSwNP were significantly higher than those in CRSsNP and controls. (2) Cellular experiments: TGF-β1 induced EMT-like transformation in PHNECs, featured by changes in cell morphology and upregulation of mesenchymal proteins and miR-21. The miR-21 inhibitor, as well as the Akt-specific inhibitor, suppressed TGF-β1-induced EMT. Mechanically, downregulation of miR-21 resulted in increased PTEN and decreased Akt phosphorylation. Furthermore, overexpression of miR-21 had the opposite effects. Conclusions: Our findings suggest that the TGF-β1-miR-21-PTEN-Akt axis may contribute to the pathogenesis of CRSwNP. miR-21 might be a reliable target for treating nasal polyp genesis through EMT suppression. Moreover, miR-21 inhibitors could be a novel class of antipolyp drug that modulates PTEN expression and Akt activation. In addition, further investigation regarding the reason underlying miR-21 overexpression in CRSwNP could provide a molecular target for novel treatment strategies for nasal polyposis.

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“…Moreover, the TGF-β1 signaling pathway has been reported to have close contact with the AhR signaling pathway, and a crosstalk might exist between AhR and TGF-β1. Recently published data revealed that AhR, which is a unique intracellular protein, might play a key role in modulating the mucosal structural integrity by regulating TGF-β1 expression [1,25]. The AhR-/- fibroblasts secreted obviously more TGF-β1 than the AhR+/+ fibroblasts, and the AhR-/- fibroblasts indicated increased activated TGF-β1 mRNA levels.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic rhinosinusitis (CRS) is a chronic inflammatory disease involving the nasal cavity and sinus mucosa, which results in a substantial burden with a prevalence of about 12.5% of the population [1]. CRS includes two types: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) [2].…”

Section: Introductionmentioning

confidence: 99%

Differential Expression of the Aryl Hydrocarbon Receptor and Transforming Growth Factor Beta 1 in Chronic Rhinosinusitis with Nasal Polyps with Allergic Rhinitis

Chen

Xiao²,

Liu³

et al. 2017

ORL

Self Cite

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Objective: This study aimed to determine the aryl hydrocarbon receptor (AhR) and transforming growth factor beta 1 (TGF-β1) expression levels in chronic rhinosinusitis (CRS) and their possible correlation with allergic state and tissue remodeling. Methods: Patients were enrolled and divided into the following groups: CRS without nasal polyps (NP) without allergic rhinitis (AR) (CRSsNPsAR; n = 20), CRS with NP with AR (CRSwNPwAR; n = 20), CRS with NP without AR (CRSwNPsAR; n = 20), and controls (n = 15). Tissue samples were analyzed by Masson trichrome staining for collagen, while the location and expression of AhR and TGF-β1 were analyzed by immunohistochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blotting. Results: The collagen amounts as well as AhR and TGF-β1 mRNA and protein expression levels were significantly increased in the CRSsNPsAR group compared with the CRSwNP (CRSwNPsAR and CRSwNPwAR) samples (p < 0.01). However, higher collagen amounts (p < 0.05) and higher TGF-β1 (p < 0.05) but lower AhR expression levels (p < 0.05) were detected in the CRSwNPwAR versus the CRSwNPsAR patients. Both AhR and TGF-β1 expression were positively correlated with the collagen level in CRS samples (p < 0.01). Conclusions: Elevated AhR expression may be involved in the progression of tissue remodeling in CRSsNPsAR similar to TGF-β1 expression. Conversely, lower AhR expression may be involved in allergic reactions in CRSwNPwAR.

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Regulation of Transforming Growth Factor-β1 Activation and Expression in the Tissue Remodeling Involved in Chronic Rhinosinusitis

Cited by 24 publications

References 75 publications

IL-5 and IL-6 are increased in the frontal recess of eosinophilic chronic rhinosinusitis patients

IL-5 and IL-6 are increased in the frontal recess of eosinophilic chronic rhinosinusitis patients

TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

Differential Expression of the Aryl Hydrocarbon Receptor and Transforming Growth Factor Beta 1 in Chronic Rhinosinusitis with Nasal Polyps with Allergic Rhinitis

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