High glucose disrupts autophagy lysosomal pathway in gingival epithelial cells via ATP6V0C

Huang, Xiaohong; Kuang, Shuhong; Shen, Zhen; Liang, Min; Zhao, Lin

doi:10.1002/jper.19-0262

Cited by 15 publications

(14 citation statements)

References 26 publications

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“…Autophagy [95] is responsible for the removal and recycling of unnecessary or dysfunctional cellular components and regulating energy and metabolic homeostasis through the autophagy lysosomal pathway (ALP) to keep the cells alive. This process can also inhibit or reduce inflammasome activation by removing the inflammatory mediators [96]. LC3 is a membrane marker for autophagosomes and autolysosomes [96].…”

Section: Cellular Debris Eliminationmentioning

confidence: 99%

“…This process can also inhibit or reduce inflammasome activation by removing the inflammatory mediators [96]. LC3 is a membrane marker for autophagosomes and autolysosomes [96].…”

Section: Cellular Debris Eliminationmentioning

confidence: 99%

“…Alterations in autophagy mechanisms may contribute to inflammation-associated metabolic diseases and have been related to insulin resistance development and ROSmediated autophagy by P.gingivalis induction [100]. P.gingivalis stimulation had no effect on the ALP pathway while disruption of ALP via the ATP6VOC gene and lysosomal acidity was observed in experimental studies after high glucose induction, which results in the accumulation of mature IL-1β, keeping the inflammatory response and increasing periodontal destruction [96].…”

Section: Cellular Debris Eliminationmentioning

confidence: 99%

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Diabetes Mellitus and Periodontitis Share Intracellular Disorders as the Main Meeting Point

Portes

Bullón

Quiles

et al. 2021

Cells

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Diabetes and periodontitis are two of the most prevalent diseases worldwide that negatively impact the quality of life of the individual suffering from them. They are part of the chronic inflammatory disease group or, as recently mentioned, non-communicable diseases, with inflammation being the meeting point among them. Inflammation hitherto includes vascular and tissue changes, but new technologies provide data at the intracellular level that could explain how the cells respond to the aggression more clearly. This review aims to emphasize the molecular pathophysiological mechanisms in patients with type 2 diabetes mellitus and periodontitis, which are marked by different impaired central regulators including mitochondrial dysfunction, impaired immune system and autophagy pathways, oxidative stress, and the crosstalk between adenosine monophosphate-activated protein kinase (AMPK) and the renin-angiotensin system (RAS). All of them are the shared background behind both diseases that could explain its relationship. These should be taken in consideration if we would like to improve the treatment outcomes. Currently, the main treatment strategies in diabetes try to reduce glycemia index as the most important aspect, and in periodontitis try to reduce the presence of oral bacteria. We propose to add to the therapeutic guidelines the handling of all the intracellular disorders to try to obtain better treatment success.

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Section: Cellular Debris Eliminationmentioning

confidence: 99%

“…This process can also inhibit or reduce inflammasome activation by removing the inflammatory mediators [96]. LC3 is a membrane marker for autophagosomes and autolysosomes [96].…”

Section: Cellular Debris Eliminationmentioning

confidence: 99%

Section: Cellular Debris Eliminationmentioning

confidence: 99%

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Diabetes Mellitus and Periodontitis Share Intracellular Disorders as the Main Meeting Point

Portes

Bullón

Quiles

et al. 2021

Cells

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“…RNA-seq data of the gingival epithelium of mice with periodontitis with diabetes mellitus and mice with periodontitis were obtained as we reported before [23]. Bioinformatic analysis were processed and executed by RStudio software and limma [24] package.…”

Section: Bioinformatic Analysismentioning

confidence: 99%

Regulation of the unfolded protein response transducer IRE1α by SERPINH1 aggravates periodontitis with diabetes mellitus via prolonged ER stress

Huang

Zhang

et al. 2022

Cellular Signalling

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BackgroundThe hyperglycemic microenvironment induced by diabetes mellitus aggravates the in ammatory response, in which the inositol-requiring enzyme-1α (IRE1α) signal transduction pathway of the unfolded protein response (UPR) participates. This study aimed to investigate the mechanism by which hyperglycemia regulates the IRE1α signaling pathway and affects endoplasmic reticulum (ER) homeostasis in human gingival epithelium in periodontitis with diabetes mellitus (DP). MethodsHuman gingival epithelium samples from healthy subjects, subjects with periodontitis and subjects with DP were collected, in vitro cultures of human gingival epithelial cells were challenged with a hyperglycemic microenvironment to observe the effects of diabetes on periodontal in ammation and to assess UPR-IRE1α signaling in human gingival epithelium in DP. Subsequently, RNA sequencing (RNAseq) data was analyzed to investigate the expression of ER-related genes in human gingival epithelium.Furthermore, to explore the key role of serpin family H member 1 (SERPINH1) in the regulation of UPR-IRE1α signaling in a hyperglycemic microenvironment, experiments in SERPINH1-knockdown and SERPINH1-overexpression models were established in vitro. ResultsDiabetes causes a hyperin ammatory response in human gingival epithelium, which accelerates periodontal in ammation. A hyperglycemic microenvironment inhibited the inositol-requiring enzyme-1α / X-box binding protein 1 (IRE1α/XBP1) axis, decreased the expression of glucose regulated protein 78 (GRP78), and ultimately impaired the UPR, causing ER stress to be prolonged or more severe in human gingival epithelium. The RNA-seq and experiments revealed that the mechanism by which periodontitis is aggravated in individuals with diabetes mellitus may involve decreased SERPINH1 expression. SERPINH1 might act as an activator of IRE1α, maintaining human gingival epithelium homeostasis, suppressing nuclear factor-κB signaling pathway and reducing NOD-like receptor, pyrin domain containing protein 3 (NLRP3) and interleukin-1 beta (IL-1β) expression by preventing prolonged ER stress induced by highglucose conditions. ConclusionRegulation of the UPR transducer IRE1α by SERPINH1 alleviates DP by mitigating prolonged ER stress.

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“…Furthermore, inhibiting autophagy could enhance inflammation. Huang et al (Huang et al, 2020) found high glucose environment could disrupt the autophagy lysosomal pathway (ALP) via a special subunit on the ATPase transmembrane (ATP6V0C), consequently enhancing the expression of IL-1b in HGECs.…”

Section: Ats-1 Hek 293mentioning

confidence: 99%

Interaction Between Autophagy and Porphyromonas gingivalis-Induced Inflammation

Kang

Dai²,

Wang³

et al. 2022

Front. Cell. Infect. Microbiol.

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Autophagy is an immune homeostasis process induced by multiple intracellular and extracellular signals. Inflammation is a protective response to harmful stimuli such as pathogen microbial infection and body tissue damage. Porphyromonas gingivalis infection elicits both autophagy and inflammation, and dysregulation of autophagy and inflammation promotes pathology. This review focuses on the interaction between autophagy and inflammation caused by Porphyromonas gingivalis infection, aiming to elaborate on the possible mechanism involved in the interaction.

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High glucose disrupts autophagy lysosomal pathway in gingival epithelial cells via ATP6V0C

Cited by 15 publications

References 26 publications

Diabetes Mellitus and Periodontitis Share Intracellular Disorders as the Main Meeting Point

Diabetes Mellitus and Periodontitis Share Intracellular Disorders as the Main Meeting Point

Regulation of the unfolded protein response transducer IRE1α by SERPINH1 aggravates periodontitis with diabetes mellitus via prolonged ER stress

Interaction Between Autophagy and Porphyromonas gingivalis-Induced Inflammation

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