Tubulointerstitial nephritis antigen-like 1 is a novel matricellular protein that promotes gastric bacterial colonization and gastritis in the setting of Helicobacter pylori infection

Teng, Yong‐Sheng; Xie, Rui; Xu, Jingyu; Wang, Pan; Chen, Wanyan; Shan, Zhi‐Guo; Yan, Zong‐Bao; Mao, Fang‐Yuan; Cheng, Ping; Li, Peng; Zhang, Jinyu; Tian, Wenqing; Yang, Shi‐Ming; Zhao, Yongliang; Chen, Weisan; Zou, Quanming; Zhuang, Yuan

doi:10.1038/s41423-023-01055-4

Cited by 4 publications

(4 citation statements)

References 50 publications

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“…6 D), along with high ITGAV expression by monocytes in Human Protein Atlas (HPA) immune cell dataset (Fig. S16 A), implied that ANGPTL4 probably induced monocytes to produce CCL5 by binding to ITGAV to activate phosphoinositide 3-kinase (PI3K)–AKT–NF-κB signaling pathway [ 10 , 29 ]. Moreover, signaling pathway blocking experiments revealed that ANGPTL4 and cANGPTL4 significantly induced CCL5 via PI3K–AKT–NF-κB (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…7 A), and high expressions of ITGAV on T regs from HPA immune cell dataset (Fig. S16 A) implied that ANGPTL4 might have effects on T regs by binding to ITGAV to activate PI3K–AKT–NF-κB signaling pathway [ 10 , 29 ]. ANGPTL4-treated T regs and cANGPTL4-treated T regs showed activated PI3K–AKT–NF-κB signaling pathways (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…As the first-contacted cells infected by H. pylori within the gastric mucosa, gastric epithelial cells (GECs) are believed to be the major effector cells modulated by H. pylori to secrete proinflammatory molecules that regulate a biased inflammatory response [ 7 , 8 ]. Moreover, the biological activities of several inflammatory factors, including matrix metalloproteinases and matricellular proteins, could also change immune cell infiltration shown in H. pylori infection [ 9 , 10 ]. However, potential factors that induce largely mononuclear cell infiltration, rather than granulocytes during H. pylori infection, are not yet identified.…”

Section: Introductionmentioning

confidence: 99%

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Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis

Xie,

You,

Chen

et al. 2024

Research

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Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori -associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA -dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a −/− , Angptl4 −/− , and Il17a −/− Angptl4 −/− mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K–AKT–NF-κB, resulting in increased gastric influx of regulatory CD4 + T cells (T regs ) via CCL5–CCR4-dependent migration. In turn, ANGPTL4 induced T reg proliferation by binding to ITGAV to activate PI3K–AKT–NF-κB, promoting H. pylori -associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis

Xie,

You,

Chen

et al. 2024

Research

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“…2e), likely re ecting the invasion of immune cells 50,51 . Several of the detected proteins are also upregulated in other in ammatory intestinal diseases: extracellular matrix protein 1 (ECM1), which was reported to be elevated in in ammatory bowel disease (IBD) 52 and tubulointerstitial nephritis antigen like 1 (Tinagl1), a matricellular protein with protease activity upregulated in gastric cancer and involved in MMP regulation 53 , as well as in Heliobacter pylori induced gastritis 54 . Together with Tinagl1, other proteins with proteolytic activity such as plasminogen (Plg), furin and proteasome subunit beta type 8 (Psmb8) were also upregulated (Fig.…”

Section: Protein Abundances Change In a Tissue Layer-speci C Manner U...mentioning

confidence: 99%

Relaxation of mucosal fibronectin fibers in late gut inflammation following neutrophil infiltration in mice

Rappold,

Kalogeropoulus,

Keller

et al. 2024

Preprint

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The continuously remodeled extracellular matrix (ECM) plays a pivotal role in gastrointestinal health and disease, yet its precise functions remain elusive. In this study, we employed laser capture microdissection combined with low-input proteomics to investigate ECM remodeling during Salmonella-driven inflammation. We also probed the mechanosensitive state of fibronectin, a crucial ECM component with diverse functions dependent on its tensile state. While fibronectin fibers in healthy intestinal tissue are typically stretched, we demonstrated their relaxation only hours after infection in intestinal smooth muscles, despite the absence of bacteria in that area. In contrast, within the mucosa, where Salmonella is present starting 12 hours post-infection, fibronectin fiber relaxation occured exclusively during late-stage infection at 72 hours, and was localized to neutrophil clusters. Using N-terminomics, we identified three new cleavage sites in fibronectin in the inflamed cecum. Our work suggests that the ECM remodeling responses of different tissue layers in the intestine are distinct and carefully orchestrated.

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Association of oxidative balance score with Helicobacter pylori infection and mortality among US population

Peng,

Sun,

Zhu

et al. 2024

Eur J Nutr

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Tubulointerstitial nephritis antigen-like 1 is a novel matricellular protein that promotes gastric bacterial colonization and gastritis in the setting of Helicobacter pylori infection

Cited by 4 publications

References 50 publications

Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis

Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis

Relaxation of mucosal fibronectin fibers in late gut inflammation following neutrophil infiltration in mice

Association of oxidative balance score with Helicobacter pylori infection and mortality among US population

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