Cigarette smoke extract-induced p120-mediated NF-κB activation in human epithelial cells is dependent on the RhoA/ROCK pathway

Zhang, Chao; Qin, Shenghui; Qin, Lingzhi; Liu, Liwei; Sun, Wenjia; Li, Xiyu; Li, Naping; Wu, Renliang; Xi, Wang

doi:10.1038/srep23131

Cited by 28 publications

(18 citation statements)

References 42 publications

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“…To further study the inflammatory responses, we measured the protein abundance of NF-κB (p50/p105) in both female and male mice. The activation of NF-κB is well documented in different lung injury models [44] including cigarette smoke-induced inflammation, wheras research on e-cig aerosol induced NF-κB activation remains less explored [45][46][47][48]. Although the anti-inflammatory effects (i.e.…”

Section: Discussionmentioning

confidence: 99%

E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation

Wang

Sundar

et al. 2020

Respir Res

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Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanisms that mediate toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChRα7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lung tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased proinflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRα7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8 and MMP9, were altered both at the protein and mRNA transcript levels in female and male KO mice, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChRα7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin, significantly in a sex-dependent manner, but without the direct role of nAChRα7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChRα7 in a sex-dependent manner.

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Section: Discussionmentioning

confidence: 99%

E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation

Wang

Sundar

et al. 2020

Respir Res

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“…To further study the inflammatory responses, we measured the protein abundance of NF-κB (p50/p105) in both female and male mice. The activation of NF-κB is well documented in inflammatory responses, especially in cigarette smoke-induced inflammation, however research on e-cig aerosolrelated NF-κB dysregulation is relatively scarce [42,43]. Interestingly, while the anti-inflammatory effects (i.e.…”

Section: Discussionmentioning

confidence: 99%

E-cigarette-Induced Pulmonary Inflammation and Dysregulated Repair are Mediated by nAChR α7 Receptor

Wang¹,

Sundar²,

Li³

et al. 2020

Preprint

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Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has conducted to understand the mechanism of toxicological and pulmonary effects of e-cigs. We hypothesized that sub-chronic exposure of e-cigs induced inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChR α7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial-cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lungs were collected for determination of inflammatory responses and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased the lung influx of macrophages and T-lymphocytes, and the levels of pro-inflammatory cytokines, while nAChR α7 knockdown blocked the inflammatory responses. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8, and MMP9, in both sex mice were altered at both protein and gene levels when WT mice were exposed to PG alone in a sex-dependent manner. Moreover, MMP12 increased significantly in male mice exposed to PG with or without nicotine in a nAChR α7 dependent manner.Additionally, the abundance of ECM proteins, such as collagen and fibronectin, was significantly altered after sub-chronic e-cig exposure with or without nicotine in a sex-dependent manner, but nAChR α7 independent manner. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChR α7 in a sexdependent manner. electronic cigarette aerosol and inhaled nicotine effects on periodontal and pulmonary tissues. Oral Dis 2017, 23:1052-1057. 3. Kaur G, Muthumalage T, Rahman I: Mechanisms of toxicity and biomarkers of flavoring and flavor enhancing chemicals in emerging tobacco and nontobacco products. Toxicol Lett 2018, 288:143-155.4.

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“…[ 38 ] demonstrated that miR-223 acts as a pro-inflammatory factor in inflammatory bowel disease, a premalignant lesion that can lead to colon cancer, by targeting claudin 8 (CLDN8). Our previous study demonstrated that reduced p120 expression causes inflammation by activating RhoA and regulating NF-κB signaling [ 39 , 40 ]. Inflammation and cancer are inextricably linked, and abnormal inflammatory responses can initiate tumor development.…”

Section: Discussionmentioning

confidence: 99%

miR-223 promotes colon cancer by directly targeting p120 catenin

Liu

Zhang

et al. 2017

Oncotarget

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microRNA (miRNA) dysregulation is frequently observed in colon cancer. Previous studies found that miR-223 is upregulated in colon cancer and functions as an oncogene. Conversely, p120 is often downregulated or even absent in colon cancer, and is a likely tumor suppressor. The present study showed that increased miR-223 and decreased p120 levels are associated with colon cancer malignancy, and p120 expression is negatively correlated with miR-223 expression. A dual luciferase reporter assay showed that miR-223 directly targets p120. miR-223 upregulation in a colon cancer cell line upregulated c-Myc, cyclinD1, MMP7, and vimentin expression, downregulated E-cadherin, increased nuclear expression of β-catenin, and enhanced RhoA activation. We suggest miR-223 may promote colon cancer cell invasion and metastasis by downregulating p120, thereby reducing intercellular adhesion, promoting RhoA activity, and activating β-catenin signaling. Thus miR-223 functions as an oncogene in colon cancer and may be a potential diagnostic and therapeutic target for anti-colon cancer treatment.

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Cigarette smoke extract-induced p120-mediated NF-κB activation in human epithelial cells is dependent on the RhoA/ROCK pathway

Cited by 28 publications

References 42 publications

E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation

E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation

E-cigarette-Induced Pulmonary Inflammation and Dysregulated Repair are Mediated by nAChR α7 Receptor

miR-223 promotes colon cancer by directly targeting p120 catenin

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