Roles of TRPM4 in immune responses in keratinocytes and identification of a novel TRPM4-activating agent

Saito, Kaori; Fujita, Fumitaka; Toriyama, Manami; Utami, Ratna Annisa; Guo, Zhihan; Murakami, Masato; Kato, Hiroko; Suzuki, Yoshiro; Okada, Fumihiro; Tominaga, Makoto; Ishii, Ken J.

doi:10.1016/j.bbrc.2023.02.062

Cited by 2 publications

(2 citation statements)

References 46 publications

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“…The most upregulated DEGs (25 at 8h and 52 at 24h) were reported to be involved in the global regulation of skin homeostasis such as Late Cornified Envelope 2C 33 and A ( LCE2C and LCE2A ) 34 , pepiplakin-1 ( EPPK1 ), the protease inhibitor Serpin Family B Member 13 ( SERPINB13 ) 35 , Aspartate Beta-Hydroxylase Domain Containing 2 ( ASPHD2 ), Lanosterol Synthase ( LSS ) and Arachidonic acid 12-lipoxygenase ( ALOX12 ). A large proportion of the other DEGs was associated with the activation of the immune response in keratinocytes, RNA processing, vascular response, and stress in keratinocytes such as thermo-sensitive transient receptor potential M4 ( TRPM4 ) 36 , Cleavage and polyadenylation specificity factor subunit 1 ( CPSF1 ) 37 , Metallothionein-1G ( MT1G ) and Calmodulin-like protein 5 ( CALML5 ) 38 , respectively. Interestingly, upon injection of the COVID-19 vaccine, we found a global downregulation of IL-6 signaling (i.e., Il6, IL6R ) and a conserved strong expression of genes associated with the transport of lipoprotein, such as low-density lipoprotein receptor ( LDLR ) and low-density lipoprotein receptor-related protein 8 ( LRP8 ), two pathways previously suggested to be involved in LNP particle incorporation 39 .…”

Section: Resultsmentioning

confidence: 99%

Multi-modal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine

Scholaert,

Peries,

Braun

et al. 2023

Preprint

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The field of vaccination is witnessing a remarkable surge in the development of innovative strategies. There is a need to develop technological platforms capable of generating human data prior to progressing to clinical trials. Here we introduce VaxSkin, a flexible solution designed for the comprehensive monitoring of the natural human skin ecosystem’s response to vaccines over time. Based on bioengineering to repurpose surgical resections, it allows a comprehensive analysis of the response to vaccines at both organ and single-cell levels. Upon injection of the mRNA-1273 COVID-19 vaccine, we characterized precise sequential molecular events triggered upon detection of the exogenous substance. We also found that the vaccine consistently targets DC/macrophages and mast cells, regardless of the administration route, while promoting specific cell-cell communications in surrounding immune cell subsets. Given its direct translational relevance, VaxSkin provides a multiscale vision of skin vaccination that could pave the way toward the development of new vaccination development strategies.

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Section: Resultsmentioning

confidence: 99%

Multi-modal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine

Scholaert,

Peries,

Braun

et al. 2023

Preprint

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“…This interaction occurs in dendritic and immune cells, including T lymphocytes and mast cells, and contributes to cellular functions [ 11 - 15 ]. Due to its widespread expression and diverse functional roles in different cell types, TRPM4 has been implicated in the pathophysiology of various cardiovascular and immune diseases [ 16 - 18 ].…”

Section: Introductionmentioning

confidence: 99%

Monitoring trafficking and expression of hemagglutinin-tagged transient receptor potential melastatin 4 channel in mammalian cells

Hwang

Lee

Byun

et al. 2023

Korean J Physiol Pharmacol

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The TRPM4 gene encodes a Ca 2+ -activated monovalent cation channel called transient receptor potential melastatin 4 (TRPM4) that is expressed in various tissues. Dysregulation or abnormal expression of TRPM4 has been linked to a range of diseases. We introduced the hemagglutinin (HA) tag into the extracellular S6 loop of TRPM4, resulting in an HA-tagged version called TRPM4-HA. This TRPM4-HA was developed to investigate the purification, localization, and function of TRPM4 in different physiological and pathological conditions. TRPM4-HA was successfully expressed in the intact cell membrane and exhibited similar electrophysiological properties, such as the current-voltage relationship, rapid desensitization, and current size, compared to the wild-type TRPM4. The presence of the TRPM4 inhibitor 9-phenanthrol did not affect these properties. Furthermore, a wound-healing assay showed that TRPM4-HA induced cell proliferation and migration, similar to the native TRPM4. Co-expression of protein tyrosine phosphatase, non-receptor type 6 (PTPN6 or SHP-1) with TRPM4-HA led to the translocation of TRPM4-HA to the cytosol. To investigate the interaction between PTPN6 and tyrosine residues of TRPM4 in enhancing channel activity, we generated four mutants in which tyrosine (Y) residues were substituted with phenylalanine (F) at the N-terminus of TRPM4. The YF mutants displayed properties and functions similar to TRPM4-HA, except for the Y256F mutant, which showed resistance to 9-phenanthrol, suggesting that Y256 may be involved in the binding site for 9-phenanthrol. Overall, the creation of HA-tagged TRPM4 provides researchers with a valuable tool to study the role of TRPM4 in different conditions and its potential interactions with other proteins, such as PTPN6.

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Roles of TRPM4 in immune responses in keratinocytes and identification of a novel TRPM4-activating agent

Cited by 2 publications

References 46 publications

Multi-modal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine

Multi-modal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine

Monitoring trafficking and expression of hemagglutinin-tagged transient receptor potential melastatin 4 channel in mammalian cells

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