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Article: Vitamin D3 activates the autolysosomal degradation function against Helicobacter pylori through the PDIA3 receptor in gastric epithelial cells

TitleVitamin D3 activates the autolysosomal degradation function against Helicobacter pylori through the PDIA3 receptor in gastric epithelial cells
Authors
KeywordsAutophagy
calcium
Helicobacter pylor
ilysosome
PDIA3
Issue Date2019
PublisherTaylor & Francis: STM, Behavioural Science and Public Health Titles. The Journal's web site is located at http://www.tandfonline.com/loi/kaup20#.VfwhQUaFOnI
Citation
Autophagy, 2019, v. 15 n. 4, p. 707-725 How to Cite?
AbstractHelicobacter pylori (H. pylori) is a common human pathogenic bacterium. Once infected, it is difficult for the host to clear this organism using the innate immune system. Increased antibiotic resistance further makes it challenging for effective eradication. However, the mechanisms of immune evasion still remain obscure, and novel strategies should be developed to efficiently eliminate H. pylori infection in stomachs. Here we uncovered desirable anti-H. pylori effect of vitamin D3 both in vitro and in vivo, even against antibiotic-resistant strains. We showed that H. pylori can invade into the gastric epithelium where they became sequestered and survived in autophagosomes with impaired lysosomal acidification. Vitamin D3 treatment caused a restored lysosomal degradation function by activating the PDIA3 receptor, thereby promoting the nuclear translocation of PDIA3-STAT3 protein complex and the subsequent upregulation of MCOLN3 channels, resulting in an enhanced Ca2+ release from lysosomes and normalized lysosomal acidification. The recovered lysosomal degradation function drives H. pylori to be eliminated through the autolysosomal pathway. These findings provide a novel pathogenic mechanism on how H. pylori can survive in the gastric epithelium, and a unique pathway for vitamin D3 to reactivate the autolysosomal degradation function, which is critical for the antibacterial action of vitamin D3 both in cells and in animals, and perhaps further in humans.
Persistent Identifierhttp://hdl.handle.net/10722/290609
ISSN
2023 Impact Factor: 14.6
2023 SCImago Journal Rankings: 4.035
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHu, W-
dc.contributor.authorZhang, L-
dc.contributor.authorLi, MX-
dc.contributor.authorShen, J-
dc.contributor.authorLiu, XD-
dc.contributor.authorXiao, ZG-
dc.contributor.authorwu, DL-
dc.contributor.authorHo, IHT-
dc.contributor.authorWu, JCY-
dc.contributor.authorCheung, CKY-
dc.contributor.authorZhang, YC-
dc.contributor.authorLau, AHY-
dc.contributor.authorAshktorab, H-
dc.contributor.authorSmoot, DT-
dc.contributor.authorFang, EF-
dc.contributor.authorChan, MTV-
dc.contributor.authorGin, T-
dc.contributor.authorGong, W-
dc.contributor.authorWu, WKK-
dc.contributor.authorCho, CH-
dc.date.accessioned2020-11-02T05:44:39Z-
dc.date.available2020-11-02T05:44:39Z-
dc.date.issued2019-
dc.identifier.citationAutophagy, 2019, v. 15 n. 4, p. 707-725-
dc.identifier.issn1554-8627-
dc.identifier.urihttp://hdl.handle.net/10722/290609-
dc.description.abstractHelicobacter pylori (H. pylori) is a common human pathogenic bacterium. Once infected, it is difficult for the host to clear this organism using the innate immune system. Increased antibiotic resistance further makes it challenging for effective eradication. However, the mechanisms of immune evasion still remain obscure, and novel strategies should be developed to efficiently eliminate H. pylori infection in stomachs. Here we uncovered desirable anti-H. pylori effect of vitamin D3 both in vitro and in vivo, even against antibiotic-resistant strains. We showed that H. pylori can invade into the gastric epithelium where they became sequestered and survived in autophagosomes with impaired lysosomal acidification. Vitamin D3 treatment caused a restored lysosomal degradation function by activating the PDIA3 receptor, thereby promoting the nuclear translocation of PDIA3-STAT3 protein complex and the subsequent upregulation of MCOLN3 channels, resulting in an enhanced Ca2+ release from lysosomes and normalized lysosomal acidification. The recovered lysosomal degradation function drives H. pylori to be eliminated through the autolysosomal pathway. These findings provide a novel pathogenic mechanism on how H. pylori can survive in the gastric epithelium, and a unique pathway for vitamin D3 to reactivate the autolysosomal degradation function, which is critical for the antibacterial action of vitamin D3 both in cells and in animals, and perhaps further in humans.-
dc.languageeng-
dc.publisherTaylor & Francis: STM, Behavioural Science and Public Health Titles. The Journal's web site is located at http://www.tandfonline.com/loi/kaup20#.VfwhQUaFOnI-
dc.relation.ispartofAutophagy-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAutophagy-
dc.subjectcalcium-
dc.subjectHelicobacter pylor-
dc.subjectilysosome-
dc.subjectPDIA3-
dc.titleVitamin D3 activates the autolysosomal degradation function against Helicobacter pylori through the PDIA3 receptor in gastric epithelial cells-
dc.typeArticle-
dc.identifier.emailCheung, CKY: ckyc@hku.hk-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1080/15548627.2018.1557835-
dc.identifier.pmid30612517-
dc.identifier.pmcidPMC6526874-
dc.identifier.scopuseid_2-s2.0-85059650294-
dc.identifier.hkuros318311-
dc.identifier.volume15-
dc.identifier.issue4-
dc.identifier.spage707-
dc.identifier.epage725-
dc.identifier.isiWOS:000462521900010-
dc.publisher.placeUnited States-
dc.identifier.issnl1554-8627-

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