Pharmaco-Optogenetic Targeting of TRPC Activity Allows for Precise Control Over Mast Cell NFAT Signaling

Bacsa, Bernadett; Graziani, Annarita; Krivić, Denis; Wiedner, Patrick; Malli, Roland; Rauter, Thomas; Tiapko, Oleksandra

doi:10.3389/fimmu.2020.613194

Cited by 3 publications

(1 citation statement)

References 38 publications

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“…The cyclic adenosine monophosphate (cAMP) signalling pathway, a well-known downstream mediator of MrgprB/X2, indirectly triggers Ca 2+ release from intracellular stores, which may not be sufficient to induce rapid MrgprB/X2-mediated Ca 2+ elevation. Recent studies have shown that transient receptor potential canonical (TRPC) channels may contribute to MrgprB2-mediated mast cell activation independently of the FcεRI pathway [ 58 , 59 ]. However, further mechanistic studies are required.…”

Section: Discussionmentioning

confidence: 99%

PACAP38/mast-cell-specific receptor axis mediates repetitive stress-induced headache in mice

Son,

Zhang,

Shannonhouse

et al. 2024

J Headache Pain

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Background Pain, an evolutionarily conserved warning system, lets us recognize threats and motivates us to adapt to those threats. Headache pain from migraine affects approximately 15% of the global population. However, the identity of any putative threat that migraine or headache warns us to avoid is unknown because migraine pathogenesis is poorly understood. Here, we show that a stress-induced increase in pituitary adenylate cyclase-activating polypeptide-38 (PACAP38), known as an initiator of allosteric load inducing unbalanced homeostasis, causes headache-like behaviour in male mice via mas-related G protein-coupled receptor B2 (MrgprB2) in mast cells. Methods The repetitive stress model and dural injection of PACAP38 were performed to induce headache behaviours. We assessed headache behaviours using the facial von Frey test and the grimace scale in wild-type and MrgprB2-deficient mice. We further examined the activities of trigeminal ganglion neurons using in vivo Pirt-GCaMP Ca2+ imaging of intact trigeminal ganglion (TG). Results Repetitive stress and dural injection of PACAP38 induced MrgprB2-dependent headache behaviours. Blood levels of PACAP38 were increased after repetitive stress. PACAP38/MrgprB2-induced mast cell degranulation sensitizes the trigeminovascular system in dura mater. Moreover, using in vivo intact TG Pirt-GCaMP Ca2+ imaging, we show that stress or/and elevation of PACAP38 sensitized the TG neurons via MrgprB2. MrgprB2-deficient mice showed no sensitization of TG neurons or mast cell activation. We found that repetitive stress and dural injection of PACAP38 induced headache behaviour through TNF-a and TRPV1 pathways. Conclusions Our findings highlight the PACAP38-MrgprB2 pathway as a new target for the treatment of stress-related migraine headache. Furthermore, our results pertaining to stress interoception via the MrgprB2/PACAP38 axis suggests that migraine headache warns us of stress-induced homeostatic imbalance.

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Section: Discussionmentioning

confidence: 99%

PACAP38/mast-cell-specific receptor axis mediates repetitive stress-induced headache in mice

Son,

Zhang,

Shannonhouse

et al. 2024

J Headache Pain

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Quercetin and Kaempferol inhibit HMC-1 activation via SOCE/NFATc2 signaling and suppress hippocampal mast cell activation in lipopolysaccharide-induced depressive mice

Su,

Li,

Yan

et al. 2024

Inflamm. Res.

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Identification of diagnostic biomarkers and potential therapeutic drugs in focal segmental glomerulosclerosis with metabolic syndrome by integrating bioinformatics and machine learning

Yao,

Wang,

Han

et al. 2024

Preprint

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Purpose Immune system dysregulation plays a pivotal role in focal segmental glomerulosclerosis (FSGS) and metabolic syndrome (MS). This study aimed to identify core diagnostic genes and potential therapeutic drugs for FSGS patients with MS. Methods We obtained two FSGS and one MS datasets from the GEO database. DEGs and module gene were identified via Limma and WGCNA. Then, functional enrichment analysis, PPI network construction, and machine learning algorithms were applied to identify and analyze immune-associated genes. Afterwards, the nomogram and ROC curve were used to evaluate the diagnostic value and screen core genes. Finally, immune cell dysregulation was investigated in FSGS, and connectivity map (cMAP) analysis was conducted to identify potential therapeutic small molecule compounds. Results MS dataset yielded 756 DEGs, and the integrated FSGS datasets yielded 5257 module genes. 133 genes were identified from the intersection of MS and FSGS. Following the construction of PPI network, 42 node genes were filtered. Then, eight hub genes were obtained through machine learning screening, which were further evaluated by nomogram and diagnostic value. Among them, six core genes had high diagnostic values. FSGS patients had a higher level of resting natural killer cells, monocytes, and activated dendritic cells and meanwhile lower levels of plasma cells, follicular helper T cells, resting dendritic cells, and resting mast cells. Finally, through cMAP analysis, we identified ten small molecule compounds that might work as the potential therapeutic drugs for FSGS patients with MS. Conclusion Six immune-related core genes were identified (STAT3, CX3CR1, CCDC148, TRPC6, CLMP, and CDC42EP1), and ten small molecule compounds were obtained. This study could provide core diagnostic genes and potential therapeutic compounds for FSGS patients with MS.

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Pharmaco-Optogenetic Targeting of TRPC Activity Allows for Precise Control Over Mast Cell NFAT Signaling

Cited by 3 publications

References 38 publications

PACAP38/mast-cell-specific receptor axis mediates repetitive stress-induced headache in mice

PACAP38/mast-cell-specific receptor axis mediates repetitive stress-induced headache in mice

Quercetin and Kaempferol inhibit HMC-1 activation via SOCE/NFATc2 signaling and suppress hippocampal mast cell activation in lipopolysaccharide-induced depressive mice

Identification of diagnostic biomarkers and potential therapeutic drugs in focal segmental glomerulosclerosis with metabolic syndrome by integrating bioinformatics and machine learning

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