Par2

BACKGROUND AND PURPOSE: Chymotrypsin is a pancreatic protease secreted into the lumen of the small intestine to digest food proteins. We hypothesized that chymotrypsin activity may be found close to epithelial cells and that chymotrypsin signals to them via protease-activated receptors (PARs). We deciphered molecular pharmacological mechanisms and gene expression regulation for chymotrypsin signalling in intestinal epithelial cells. EXPERIMENTAL APPROACH: The presence and activity of chymotrypsin were evaluated by Western blot and enzymatic activity tests in the luminal and mucosal compartments of murine and human gut samples...

Tendon injury produces intractable pain and disability in movement, but the medications for analgesia and restoring functional integrity of tendon are still limited. In this study, we report that proteinase-activated receptor 2 (PAR2) activation in dorsal root ganglion (DRG) neurons contributes to chronic pain and tendon histopathological changes produced by Achilles tendon partial transection injury (TTI). Tendon partial transection injury increases the expression of PAR2 protein in both somata of DRG neurons and their peripheral terminals within the injured Achilles tendon...

Fibrosis characterized by intestinal strictures is a common complication of Crohn's disease (CD), without specific antifibrotic drugs, which usually relies on surgical intervention. The transcription factor XBP1, a key component of endoplasmic reticulum (ER) stress, is required for degranulation of mast cells and linked to PAR2 activation and fibrosis. Many studies have confirmed that naringin (NAR) can inhibit ER stress and reduce organ fibrosis. We hypothesized that ER stress activated the PAR2-induced epithelial-mesenchymal transition process by stimulating mast cell degranulation to release tryptase and led to intestinal fibrosis in CD patients; NAR might play an antifibrotic role by inhibiting ER stress-induced PAR2 activation...

No abstract text is available yet for this article.

Trypanosoma cruzi is the causative agent of Chagas disease, a chronic pathology that affects the heart and/or digestive system. This parasite invades and multiplies in virtually all nucleated cells, using a variety of host cell receptors for infection. T. cruzi has a gene that encodes an ecotin-like inhibitor of serine peptidases, ISP2. We generated ISP2-null mutants (Δisp2) in T. cruzi Dm28c using CRISPR/Cas9. Epimastigotes of Δisp2 grew normally in vitro but were more susceptible to lysis by human serum compared to parental and ISP2 add-back lines...

Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases, immune cell infiltration and protease-driven tissue damages. It is an urgent need to explore potential drug strategies for mitigating lung inflammation. Protease-activated receptor 2 (PAR2) as a vital molecular target principally participates in various inflammatory diseases via intracellular signal transduction. However, it has been rarely reported about the role of PAR2 in lung inflammation...

No abstract text is available yet for this article.

The inflamed mucosa contains a complex assortment of proteases which may participate in wound healing or in the development of inflammation-associated colon cancer. We sought to determine the role of protease-activated receptor 2 (PAR2) in epithelial wound healing in both untransformed and transformed colonic epithelial cells. Monolayers of primary epithelial cells derived from organoids cultivated from patient colonic biopsies, and of the T84 colon cancer cell line, were grown to confluence, wounded in the presence of a selective PAR2-activating peptide, and healing visualized by live cell microscopy...

BACKGROUND: Accumulating evidence implicates the activation of G-protein-coupled PARs (protease-activated receptors) by coagulation proteases in the regulation of innate immune responses. METHODS: Using mouse models with genetic alterations of the PAR2 signaling platform, we have explored contributions of PAR2 signaling to infection with coxsackievirus B3, a single-stranded RNA virus provoking multiorgan tissue damage, including the heart. RESULTS: We show that PAR2 activation sustains correlates of severe morbidity-hemodynamic compromise, aggravated hypothermia, and hypoglycemia-despite intact control of the virus...

OBJECTIVES: Uncertainties remain regarding the effect of elevated glucose levels on lymphatic metastasis of cancer cells. Our study elucidated the mechanisms linking high glucose to lymphangiogenesis and lymphatic barrier-related factors and investigated the protective role of linagliptin against lymphatic barrier dysfunction. MATERIALS AND METHODS: A CAL-27-LEC co-culture system was established. Sodium fluorescein permeability assay observed lymphatic endothelial cell permeability...

Chronic itch is a common and complex symptom often associated with skin diseases like atopic dermatitis (AD). Although IL-27 is linked to AD, its role and clinical significance in itch remain undefined. We sought to investigate IL-27 function in itch using tissue specific-transgenic mice, various itch models, behaviour scoring, RNA-seq, and cytokine/kinase array. Our findings show that IL-27 receptors were overexpressed in human AD skin. Intradermal IL-27 injection failed to directly induce itch in mice, but upregulated skin PAR2 transcripts, a key factor in itch and AD...

OBJECTIVE: The serine protease inhibitor SerpinB3 has been described as critical mediator of liver fibrosis and it has been recently proposed as an additional hepatokine involved in NASH development and insulin resistance. Protease Activated Receptor 2 has been identified as a novel regulator of hepatic metabolism. A targeted therapeutic strategy for NASH has been investigated, using 1-Piperidine Propionic Acid (1-PPA), since this compound has been recently proposed as both Protease Activated Receptor 2 and SerpinB3 inhibitor...

Studying primordial events in cancer is pivotal for identifying predictive molecular indicators and for targeted intervention. While the involvement of G-protein-coupled receptors (GPCRs) in cancer is growing, GPCR-based therapies are yet rare. Here, we demonstrate the overexpression of protease-activated receptor 2 (PAR2), a GPCR member in the fallopian tubes (FTs) of high-risk BRCA carriers as compared to null in healthy tissues of FT. FTs, the origin of ovarian cancer, are known to express genes of serous tubal intraepithelial carcinoma (STICs), a precursor lesion of high-grade serous carcinoma (HGSC)...

BACKGROUND: Tissue factor (TF) activity is stringently regulated through processes termed encryption. Post-translational modification of TF and its interactions with various protein and lipid moieties allows for a multi-step de-encryption of TF and procoagulant activation. Membrane-associated guanylate kinase-with inverted configuration (MAGI) proteins are known to regulate the localisation and activity of a number of proteins including cell-surface receptors. METHODS: The interaction of TF with MAGI1 protein was examined as a means of regulating TF activity...

The management of wounds remains a significant healthcare challenge, highlighting the need for effective wound healing strategies. To address this, it is crucial to explore the molecular mechanisms underlying tissue repair as well as explore potential therapeutic approaches. Trypsin, as a serine protease, has been clinically utilized for wound healing for decades; however, it still lacks systemic investigation on its role and related mechanism. This study aimed to investigate the effects of low-dose trypsin on wound healing both in vitro and in vivo ...

Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells...

Neutrophil extracellular traps (NETs) have been implicated in several hallmarks of cancer. Among the protumor effects, NETs promote epithelial-mesenchymal transition (EMT) in different cancer models. EMT has been linked to an enhanced expression of the clotting-initiating protein, tissue factor (TF), thus favoring the metastatic potential. TF may also exert protumor effects by facilitating the activation of protease-activated receptor 2 (PAR2). Herein, we evaluated whether NETs could induce TF expression in breast cancer cells and further promote procoagulant and intracellular signaling effects via the TF/PAR2 axis...

OBJECTIVES: This study aimed to study the effect of protease-activated receptor 2 (PAR2) on the proliferation, invasion, and clone formation of lung cancer cells. It also aimed to evaluate the inhibitory effect of melittin on PAR2 and the anti-lung cancer effect of melittin combined with gefitinib. METHODS: The correlation between the co-expression of PAR2 and epithelial-mesenchymal transition (EMT) markers was analyzed. PAR2 in A549 and NCI-H1299 cells was knocked down using siRNA...

SERRATE (SE) plays an important role in many biological processes and under biotic stress resistance. However, little about the control of SE has been clarified. Here we present a method named native chromatin-associated proteome affinity by CRISPR-dCas9 (CASPA-dCas9) to holistically capture native regulators of the SE locus. Several key regulatory factors including PHYTOCHROME RAPIDLY REGULATED 2 (PAR2), WRKY DNA-binding protein 19 (WRKY19) and the MYB-family protein MYB27 of SE are identified. MYB27 recruits the long non-coding RNA-PRC2 (SEAIR-PRC2) complex for H3K27me3 deposition on exon 1 of SE and subsequently represses SE expression, while PAR2-MYB27 interaction inhibits both the binding of MYB27 on the SE promoter and the recruitment of SEAIR-PRC2 by MYB27...

BACKGROUND: Proteases secreted by Trichinella spiralis intestinal infective larvae (IIL) play an important role in larval invasion and pathogenesis. However, the mechanism through which proteases mediate larval invasion of intestinal epithelial cells (IECs) remains unclear. A novel T. spiralis trypsin (TsTryp) was identified in IIL excretory/secretory (ES) proteins. It was an early and highly expressed protease at IIL stage, and had the potential as an early diagnostic antigen. The aim of this study was to investigate the biological characteristics of this novel TsTryp, its role in larval invasion of gut epithelium, and the mechanisms involved...