The role of Glut-1 and H+/K+-ATPase expression in hyperplasia of mice laryngeal epithelium induced by pepsin

Ao, Yin-Jie; Wu, Tingting; Cao, Zijian; Zhou, Shui‐Hong; Bao, Yang‐Yang; Shen, Lianfang

doi:10.1007/s00405-021-07221-6

Cited by 4 publications

(21 citation statements)

References 30 publications

(56 reference statements)

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“…Moreover, pepsin enhanced the expression of H + /K + ATPase in the abovementioned 3-dimensional culture system, as well as in mouse laryngeal epithelial cells. 3,13 These results suggest that acidified pepsin interacts with H + /K + ATPase during the progression of VCL.…”

mentioning

confidence: 75%

“…13 We demonstrated that acidic pepsin significantly increased migration and proliferation in those cells in a 3-dimensional culture system using primary VCL cells. 3 These results suggest that pepsin plays an important role in the abnormal proliferation of leukocytes observed in VCL. We also demonstrated that the expression of H + /K + ATPase, which is responsible for gastric acid secretion, was elevated in VCL and laryngeal carcinoma.…”

mentioning

confidence: 83%

“…Recently, laryngopharyngeal reflux has attracted attention as a potential risk factor for VCL. [2][3][4][5][6][7][8] Gastric contents include gastric acid, pepsin, bile acid, pancreatin, and chyme. [8][9][10] Pepsin is an essential digestive proteolytic enzyme and the major acid component of reflux.…”

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confidence: 99%

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Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy

Chen

Zhang

Jiang

et al. 2023

Otolaryngol.--head neck surg.

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ObjectiveTo investigate the role of H+/K+ATPase in the proliferation of pepsin‐induced vocal cord leukoplakia (VCL) cells.Study DesignTranslation research.SettingAffiliated Hospital of University.MethodsImmunohistochemistry was used to detect pepsin, H+/K+ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+/K+‐ATPase distribution of VCL cells were investigated.ResultsThe levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate‐to‐severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning‐ and autophagy‐promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+/K+‐ATPase and lysosomes in VCL cells; it also mediated lysosome acidification.ConclusionPepsin and H+/K+‐ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+/K+‐ATPase.

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confidence: 75%

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confidence: 83%

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Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy

Chen

Zhang

Jiang

et al. 2023

Otolaryngol.--head neck surg.

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“…Ao et al . reported that long-term administration of pepsin to larynx led to hyperplasia of mice laryngeal epithelium [ 11 ]. In this study, pepsin content increased in VFL with the increase in the grade of dysplasia.…”

Section: Discussionmentioning

confidence: 99%

“…Pepsin can reportedly enhance the epithelial–mesenchymal transformation of laryngeal cancer cells and also promote the migration and clonogenic ability of hypopharyngeal cancer cells, contributing to the progression of laryngeal and hypopharyngeal cancers, respectively [ 9 , 10 ]. Ao et alrecently reported that long term administration of artificial pepsin-containing gastric juice to larynx induced hyperplasia of the laryngeal epithelium in normal mice [ 11 ]. Furthermore, the content of pepsin in VFL tissues has been found to be significantly higher than that in normal vocal fold tissues [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Pepsin enhances glycolysis to promote malignant transformation of vocal fold leukoplakia epithelial cells with dysplasia

Zhang

Zhou

et al. 2022

Eur Arch Otorhinolaryngol

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Purpose The mechanism underlying malignant transformation of vocal fold leukoplakia (VFL) and the precise role of the expression of pepsin in VFL remain unclear. This study aimed to investigate the effects of acidified pepsin on VFL epithelial cell growth and migration, and also identify pertinent molecular mechanisms. Methods Immunochemistry and Western blotting were performed to measure glucose transporter type 1 (GLUT1), monocarboxylate transporters 4 (MCT4), and Hexokinase-II (HK-II) expressions. Cell viability, cell cycle, apoptosis, and migration were investigated by CCK-8 assay, flow cytometry and Transwell chamber assay, respectively. Glycolysis-related contents were determined using the corresponding kits. Mitochondrial HK-II was photographed under a confocal microscope using Mito-Tracker Red. Results It was found: the expression of pepsin and proportion of pepsin+ cells in VFL increased with the increased dysplasia grade; acidified pepsin enhanced cell growth and migration capabilities of VFL epithelial cells, reduced mitochondrial respiratory chain complex I activity and oxidative phosphorylation, and enhanced aerobic glycolysis and GLUT1 expression in VFL epithelial cells; along with the transfection of GLUT1 overexpression plasmid, 18FFDG uptake, lactate secretion and growth and migration capabilities of VFL epithelial cell were increased; this effect was partially blocked by the glycolysis inhibitor 2-deoxy-glucose; acidified pepsin increased the expression of HK-II and enhanced its distribution in mitochondria of VFL epithelial cells. Conclusion It was concluded that acidified pepsin enhances VFL epithelial cell growth and migration abilities by reducing mitochondrial respiratory complex I activity and promoting metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis.

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Acidic Pepsin Affects Laryngeal Carcinoma Cell Growth and Invasion Through Glycolysis

Yu,

Li,

Bao

et al. 2024

Otolaryngol.--head neck surg.

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ObjectiveThe pathogenic mechanism underlying the effects of acidic pepsin in laryngeal cancer remains unclear. This study investigated whether acidic pepsin influences Glut‐1 expression and glycolytic activity in laryngeal carcinoma cells and whether it plays a role in the growth and migration of these cells through glycolysis.Study DesignIn vitro study.SettingA university‐affiliated hospital.MethodsLaryngeal carcinoma TU 212 and TU 686 cells were treated with acidic pepsin and 2‐deoxy‐d‐glucose (2‐DG), then transfected with Glut‐1 small interfering RNA (siRNA). Glucose uptake was detected by a radioimmunoassay counter, lactate secretion was detected by a lactic acid kit, and Glut‐1 expression was detected by western blotting. Cell viability, migration and invasion, and clonal formation were assessed using the Cell Counting Kit‐8, Transwell chamber, and clonal formation assays, respectively.ResultsAcidic pepsin significantly increased Glut‐1 expression in laryngeal carcinoma cells compared with the control group (P < .01). It also significantly enhanced 18F‐fluorodeoxyglucose (Cin/Cout) uptake, lactate secretion, cell viability, migration, invasion, and clonal formation in laryngeal carcinoma cells compared with the control group (P < .01). The glycolytic inhibitor 2‐DG and Glut‐1 siRNA significantly reversed the effects of acidic pepsin on laryngeal carcinoma cells (P < .01).ConclusionAcidic pepsin enhances the growth and migration of laryngeal carcinoma cells by upregulating Glut‐1, thus promoting glycolysis.

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The role of Glut-1 and H+/K+-ATPase expression in hyperplasia of mice laryngeal epithelium induced by pepsin

Cited by 4 publications

References 30 publications

Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy

Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy

Pepsin enhances glycolysis to promote malignant transformation of vocal fold leukoplakia epithelial cells with dysplasia

Acidic Pepsin Affects Laryngeal Carcinoma Cell Growth and Invasion Through Glycolysis

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