Academic Journal
Modulating TRPV4 Channel Activity in Pro-Inflammatory Macrophages within the 3D Tissue Analog
| العنوان: | Modulating TRPV4 Channel Activity in Pro-Inflammatory Macrophages within the 3D Tissue Analog |
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| المؤلفون: | Parto Babaniamansour, Diego Jacho, Skyler Niedzielski, Agustin Rabino, Rafael Garcia-Mata, Eda Yildirim-Ayan |
| المصدر: | Biomedicines, Vol 12, Iss 1, p 230 (2024) |
| بيانات النشر: | MDPI AG |
| سنة النشر: | 2024 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | TRPV4, macrophage, polarization, inflammation, regeneration, Biology (General), QH301-705.5 |
| الوصف: | Investigating macrophage plasticity emerges as a promising strategy for promoting tissue regeneration and can be exploited by regulating the transient receptor potential vanilloid 4 (TRPV4) channel. The TRPV4 channel responds to various stimuli including mechanical, chemical, and selective pharmacological compounds. It is well documented that treating cells such as epithelial cells and fibroblasts with a TRPV4 agonist enhances the Ca 2+ influx to the cells, which leads to secretion of pro-inflammatory cytokines, while a TRPV4 antagonist reduces both Ca 2+ influx and pro-inflammatory cytokine secretion. In this work, we investigated the effect of selective TRPV4 modulator compounds on U937-differentiated macrophages encapsulated within three-dimensional (3D) matrices. Despite offering a more physiologically relevant model than 2D cultures, pharmacological treatment of macrophages within 3D collagen matrices is largely overlooked in the literature. In this study, pro-inflammatory macrophages were treated with an agonist, 500 nM of GSK1016790A (TRPV4(+)), and an antagonist, 10 mM of RN-1734 (TRPV4(−)), to elucidate the modulation of the TRPV4 channel at both cellular and extracellular levels. To evaluate macrophage phenotypic alterations within 3D collagen matrices following TRPV4 modulator treatment, we employed structural techniques (SEM, Masson’s trichrome, and collagen hybridizing peptide (CHP) staining), quantitative morphological measures for phenotypic assessment, and genotypic methods such as quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Our data reveal that pharmacological modulation of the macrophage TRPV4 channel alters the cytoskeletal structure of macrophages and influences the 3D structure encapsulating them. Moreover, we proved that treating macrophages with a TRPV4 agonist and antagonist enhances the expression of pro- and anti-inflammatory genes, respectively, leading to the upregulation of surface markers CD80 and CD206. In the TRPV4(−) group, the CD206 gene and CD206 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2227-9059 |
| Relation: | https://www.mdpi.com/2227-9059/12/1/230; https://doaj.org/toc/2227-9059; https://doaj.org/article/696380a667b34162a2c3508ba9d76950 |
| DOI: | 10.3390/biomedicines12010230 |
| الاتاحة: | https://doi.org/10.3390/biomedicines12010230 https://doaj.org/article/696380a667b34162a2c3508ba9d76950 |
| رقم الانضمام: | edsbas.E7101F0A |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 22279059 |
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| DOI: | 10.3390/biomedicines12010230 |