Tetraspanins in the regulation of mast cell function

Orinska, Zane; Hagemann, Philipp; Hálová, Ivana; Dráber, Petr

doi:10.1007/s00430-020-00679-x

Cited by 12 publications

(6 citation statements)

References 130 publications

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“…TM4SF1, a tumor-associated protein, is widely expressed in multiple human carcinomas, is localized at the surface of the cell membrane and late endocytic organelles, and plays a vital role in cell motility [44,45] . CD63 is an important activation marker for mast cells and is highly expressed on the surface of activated mast cells [46] . Several experiments have demonstrated that the expression of CD63 is inversely correlated with the motility of various cell types, while the overexpression of TM4SF1 can decrease the expression levels of CD63 on the cell surface, suggesting a potential mechanism for the activation and migration of mast cells [45,47] .…”

Section: Discussionmentioning

confidence: 99%

Identification of three hub genes related to the prognosis of idiopathic pulmonary fibrosis using bioinformatics analysis

Wang¹,

Wang²,

Zhou³

et al. 2022

Int. J. Med. Sci.

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Background: Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease characterized by peripheral distribution of bilateral pulmonary fibrosis that is more pronounced at the base. IPF has a short median survival time and a poor prognosis. Therefore, it is necessary to identify effective prognostic indicators to guide the treatment of patients with IPF. Methods: We downloaded microarray data of bronchoalveolar lavage cells from the Gene Expression Omnibus (GEO), containing 176 IPF patients and 20 controls. The top 5,000 genes in the median absolute deviation were classified into different color modules using weighted gene co-expression network analysis (WGCNA), and the modules significantly associated with both survival time and survival status were identified as prognostic modules. We used Lasso Cox regression and multivariate Cox regression to search for hub genes related to prognosis from the differentially expressed genes (DEGs) in the prognostic modules and constructed a risk model and nomogram accordingly. Moreover, based on the risk model, we divided IPF patients into high-risk and low-risk groups to determine the biological functions and immune cell subtypes associated with the prognosis of IPF using gene set enrichment analysis and immune cell infiltration analysis. Results: A total of 153 DEGs located in the prognostic modules, three (TPST1, MRVI1, and TM4SF1) of which were eventually defined as prognostic hub genes. A risk model was constructed based on the expression levels of the three hub genes, and the accuracy of the model was evaluated using time-dependent receiver operating characteristic (ROC) curves. The areas under the curve for 1-, 2-, and 3-year survival rates were 0.862, 0.885, and 0.833, respectively. The results of enrichment analysis showed that inflammation and immune processes significantly affected the prognosis of patients with IPF. The degree of mast and natural killer (NK) cell infiltration also increases the prognostic risk of IPF. Conclusions: We identified three hub genes as independent molecular markers to predict the prognosis of patients with IPF and constructed a prognostic model that may be helpful in promoting therapeutic gains for IPF patients.

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Section: Discussionmentioning

confidence: 99%

Identification of three hub genes related to the prognosis of idiopathic pulmonary fibrosis using bioinformatics analysis

Wang¹,

Wang²,

Zhou³

et al. 2022

Int. J. Med. Sci.

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“…At the plasma membrane, they promote interactions with other membrane and intracellular proteins and lipids, to shape the organization of membrane domains. They are considered as “molecular facilitators” connecting extracellular and cytoplasmic signaling elements [ 47 ]. In this context, CD81 is known to facilitate cells adhesion or fusion in the frame of viral infection [ 48 , 49 ].…”

Section: Cd81 Biology Trafficking and Signalingmentioning

confidence: 99%

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Bailly

Thuru

2023

Cancers

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Tetraspanin CD81 plays major roles in cell-cell interactions and the regulation of cellular trafficking. This cholesterol-embarking transmembrane protein is a co-receptor for several viruses, including HCV, HIV-1 and Chikungunya virus, which exploits the large extracellular loop EC2 for cell entry. CD81 is also an anticancer target implicated in cancer cell proliferation and mobility, and in tumor metastasis. CD81 signaling contributes to the development of solid tumors (notably colorectal, liver and gastric cancers) and has been implicated in the aggressivity of B-cell lymphomas. A variety of protein partners can interact with CD81, either to regulate attachment and uptake of viruses (HCV E2, claudin-1, IFIM1) or to contribute to tumor growth and dissemination (CD19, CD44, EWI-2). CD81-protein interactions can be modulated with molecules targeting the extracellular domain of CD81, investigated as antiviral and/or anticancer agents. Several monoclonal antibodies anti-CD81 have been developed, notably mAb 5A6 active against invasion and metastasis of triple-negative breast cancer cells. CD81-EC2 can also be targeted with natural products (trachelogenin and harzianoic acids A-B) and synthetic compounds (such as benzothiazole-quinoline derivatives). They are weak CD81 binders but offer templates for the design of new compounds targeting the open EC2 loop. There is no anti-CD81 compound in clinical development at present, but this structurally well-characterized tetraspanin warrants more substantial considerations as a drug target.

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“…Axis. It was reported that changes in the MC microenvironment of the mouse peritoneum could lead to the alteration of the release of proteases, membrane signaling, and membrane receptor phenotype in MC [12]. We next attempted to examine tryptase granules by immunohistochemistry.…”

Section: Abdominal Massage Regulates the Trypase-par2-pkcεmentioning

confidence: 99%

Abdominal Massage Improves the Symptoms of Irritable Bowel Syndrome by Regulating Mast Cells via the Trypase-PAR2-PKCε Pathway in Rats

Zhang

et al. 2022

Pain Research and Management

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Background. Irritable bowel syndrome (IBS) is a clinical disease mainly characterized as a syndrome of abdominal pain and discomfort, which frequently occurs in humans aged 20–50. Abdomen massage is of great medical significance for the health of the human body, including promoting intestinal peristalsis, relieving constipation, and facilitating weight loss. However, its potential benefits in alleviating IBS and the underlying mechanisms remain elusive. Methods. In this study, we established an IBS model in rats to evaluate the effects of abdomen massage. Forty male Sprague Dawley (SD) rats were randomly assigned into 4 groups: the normal (control) group, IBS group, abdominal massage group, and abdominal massage + ketotifen treatment group (n = 10 rats in each group). Abdominal massage was performed once a day for 5 minutes for 14 days. On day 14, the rats were euthanized and the tissues were analyzed by transmission electron microscopy (TEM), immunohistochemistry or immunofluorescence staining, and laser confocal focus to visualize the micromorphology of the intestinal mucosa. The expression of TRPV1 and the release of trypase were determined by RT-qPCR and western blot. Results. We found that compared with the control group, the mast cells in the IBS group were significantly increased and the increased MC was partially decreased by an abdominal massage with or without ketotifen treatment. We also found that TRPV1 was upregulated in the IBS group. Abdominal massage with or without ketotifen treatment could attenuate the upregulation of TRPV1 in IBS. Mechanically, results of IHC and western Blot suggested that abdominal massage reduces the sensitivity of IBS by regulating the trypase-PAR2-PKCε pathway. Conclusion. Overall, our results suggested that abdominal massage produces a beneficial effect in improving the symptoms of IBS through reducing mast cell recruitment and attenuating the trypase-PAR2-PKCε pathway. Ketotifen could promote the effect of abdominal massage on IBS treatment, which can serve as a potential therapeutic strategy for IBS.

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Tetraspanins in the regulation of mast cell function

Cited by 12 publications

References 130 publications

Identification of three hub genes related to the prognosis of idiopathic pulmonary fibrosis using bioinformatics analysis

Identification of three hub genes related to the prognosis of idiopathic pulmonary fibrosis using bioinformatics analysis

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Abdominal Massage Improves the Symptoms of Irritable Bowel Syndrome by Regulating Mast Cells via the Trypase-PAR2-PKCε Pathway in Rats

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