ArticlePLoS neglected tropical diseases2024
A novel Trichinella spiralis serine proteinase disrupted gut epithelial barrier and mediated larval invasion through binding to RACK1 and activating MAPK/ERK1/2 pathway.
Article in PLoS neglected tropical diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 12 citations in OpenAlex.
- Trichinella spiralis galectin disrupts gut epithelial integrity and mediates larval invasion via acting MUC13- ROCK2/MAPK pathway.PLoS neglected tropical diseases · 2026Article
- A barrier-centered perspective on the gut-barrier-bone axis: a review of the core role of the intestinal barrier and related probiotics with nanocoatings.Archives of microbiology · 2026Review
- Vaccination of mice with Trichinella spiralis serine proteinase enhanced gut epithelial barrier and elicited a high protective immunity.PLoS neglected tropical diseases · 2026Article
- Trichinella spiralis serine proteinase enhances antibody-dependent cell-mediated (ADCC) killing of newborn larvae by driving M1 polarization via the NF-κB pathway.Parasite (Paris, France) · 2026Article
- A Trichinella spiralis Trypsin Drives Macrophage M1 Polarization and Strengthens Cytotoxicity Killing Larvae via Activating the NF-κB Pathway.Transboundary and emerging diseases · 2026Article
- Molecular characterization of a novel Trichinella spiralis aspartyl protease and its role in the larval invasion of host intestinal epithelial cells.Parasite (Paris, France) · 2026Article
- Trichinella spiralis excretory-secretory proteins induced autophagy via activating AMPK/mTOR pathway and protected gut epithelial barrier.PLoS neglected tropical diseases · 2025Article
- Aspartic protease 2 from Trichinella spiralis excretion/secretion products hydrolyzes tight junctions of intestinal epithelial cells.PLoS neglected tropical diseases · 2025Article
- The deubiquitinase USP17LA negatively regulates T-cell activation and attenuates anti-tumor immunity.EMBO reports · 2025Article
- Trichinella spiralis serine protease mediates larval invasion of gut epithelium via binding to CK8 and activating RhoA/ROCK1 pathway.PLoS neglected tropical diseases · 2025Article
- A Trichinella spiralis serine protease triggers gut epithelial apoptosis and destroys the barrier integrity to mediate larval invasion.PLoS neglected tropical diseases · 2025Article
- Trichinella spiralis excretory/secretory proteins mediated larval invasion via inducing gut epithelial apoptosis and barrier disruption.PLoS neglected tropical diseases · 2025Article
- Vaccination of mice with Trichinella spiralis C-type lectin elicited the protective immunity and enhanced gut epithelial barrier function.PLoS neglected tropical diseases · 2025Article
- A NovelInternational journal of molecular sciences · 2024Article
- Biological characteristics of a new long-chain fatty acid transport protein 1 from Trichinella spiralis and its participation in lipid metabolism, larval moulting, and development.Veterinary research · 2024Article
- RACK1 and NEK7 mediate GSDMD-dependent macrophage pyroptosis upon Streptococcus suis infection.Veterinary research · 2024Article
- Molecular Cloning, Characterization, and Expression of a Receptor for Activated Protein Kinase C1 (RACK1) Gene inBiology · 2024Article
- Biological characteristics and functions of a novel glutamate dehydrogenase from Trichinella spiralis.Parasite (Paris, France) · 2024Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGut epithelium is the first natural barrier against Trichinella spiralis larval invasion, but the mechanism by which larval penetration of gut epithelium is not completely elucidated. Previous studies showed that proteases secreted by T. spiralis intestinal infective larvae (IIL) degraded tight junctions (TJs) proteins of gut epithelium and mediated larval invasion. A new T. spiralis serine proteinase (TsSPc) was identified in the IIL surface proteins and ES proteins, rTsSPc bound to the intestinal epithelial cell (IECs) and promoted larval invasion of IECs. The aim of this study was to characterize the interacted proteins of TsSPc and IECs, and to investigate the molecular mechanisms of TsSPc mediating larval invasion of gut mucosa. METHODOLOGY/PRINCIPAL FINDING: IIFT results showed natural TsSPc was detected in infected murine intestine at 6, 12 hours post infection (hpi) and 3 dpi. The results of GST pull-down, mass spectrometry (MS) and Co-IP indicated that rTsSPc bound and interacted specifically with receptor for activated protein C kinase 1 (RACK1) in Caco-2 cells. rTsSPc did not directly hydrolyze the TJs proteins. qPCR and Western blot showed that rTsSPc up-regulated RACK1 expression, activated MAPK/ERK1/2 pathway, reduced the expression levels of gut TJs (occludin and claudin-1) and adherent protein E-cad, increased the paracellular permeability and damaged the integrity of intestinal epithelial barrier. Moreover, the RACK1 inhibitor HO and ERK1/2 pathway inhibitor PD98059 abolished the rTsSPc activating ERK1/2 pathway, they also inhibited and abrogated the rTsSPc down-regulating expression of occludin, claudin-1 and E-cad in Caco-2 monolayer and infected murine intestine, impeded larval invasion and improved intestinal epithelial integrity and barrier function, reduced intestinal worm burdens and alleviated intestinal inflammation.
conclusionsrTsSPc bound to RACK1 receptor in gut epithelium, activated MAPK/ERK1/2 pathway, decreased the expression of gut epithelial TJs proteins and disrupted the epithelial integrity, consequently mediated T. spiralis larval invasion of gut epithelium. The results are valuable to understand T. spiralis invasion mechanism, and TsSPc might be regarded as a vaccine target against T. spiralis invasion and infection.
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