Mechanosensitive TRPV4 channel guides maturation and organization of the bilayered mammary epithelium
Abstract Biophysical cues from the cell microenvironment are detected by mechanosensitive components at the cell surface. Such machineries convert physical information into biochemical signaling cascades within cells, subsequently leading to various cellular responses in a stimulus-dependent manner....
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-57346-x |
| _version_ | 1797247271364984832 |
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| author | Kärki Tytti Koskimäki Sanna Guenther Carla Pirhonen Jonatan Rajakylä Kaisa Tojkander Sari |
| author_facet | Kärki Tytti Koskimäki Sanna Guenther Carla Pirhonen Jonatan Rajakylä Kaisa Tojkander Sari |
| author_sort | Kärki Tytti |
| collection | DOAJ |
| description | Abstract Biophysical cues from the cell microenvironment are detected by mechanosensitive components at the cell surface. Such machineries convert physical information into biochemical signaling cascades within cells, subsequently leading to various cellular responses in a stimulus-dependent manner. At the surface of extracellular environment and cell cytoplasm exist several ion channel families that are activated by mechanical signals to direct intracellular events. One of such channel is formed by transient receptor potential cation channel subfamily V member, TRPV4 that is known to act as a mechanosensor in wide variaty of tissues and control ion-influx in a spatio-temporal way. Here we report that TRPV4 is prominently expressed in the stem/progenitor cell populations of the mammary epithelium and seems important for the lineage-specific differentiation, consequently affecting mechanical features of the mature mammary epithelium. This was evident by the lack of several markers for mature myoepithelial and luminal epithelial cells in TRPV4-depleted cell lines. Interestingly, TRPV4 expression is controlled in a tension-dependent manner and it also impacts differentation process dependently on the stiffness of the microenvironment. Furthermore, such cells in a 3D compartment were disabled to maintain normal mammosphere structures and displayed abnormal lumen formation, size of the structures and disrupted cellular junctions. Mechanosensitive TRPV4 channel therefore act as critical player in the homeostasis of normal mammary epithelium through sensing the physical environment and guiding accordingly differentiation and structural organization of the bilayered mammary epithelium. |
| first_indexed | 2024-04-24T19:56:02Z |
| format | Article |
| id | doaj.art-75dfadc8d63f4735a6b8f11dbd6f09fd |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T19:56:02Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-75dfadc8d63f4735a6b8f11dbd6f09fd2024-03-24T12:20:12ZengNature PortfolioScientific Reports2045-23222024-03-0114111510.1038/s41598-024-57346-xMechanosensitive TRPV4 channel guides maturation and organization of the bilayered mammary epitheliumKärki Tytti0Koskimäki Sanna1Guenther Carla2Pirhonen Jonatan3Rajakylä Kaisa4Tojkander Sari5Department of Applied Physics, School of Science, Aalto UniversityFaculty of Medicine and Health Technology, Tampere UniversityFaculty of Medicine and Health Technology, Tampere UniversityFaculty of Medicine and Health Technology, Tampere UniversitySchool of Social Services and Health Care, Tampere University of Applied SciencesFaculty of Medicine and Health Technology, Tampere UniversityAbstract Biophysical cues from the cell microenvironment are detected by mechanosensitive components at the cell surface. Such machineries convert physical information into biochemical signaling cascades within cells, subsequently leading to various cellular responses in a stimulus-dependent manner. At the surface of extracellular environment and cell cytoplasm exist several ion channel families that are activated by mechanical signals to direct intracellular events. One of such channel is formed by transient receptor potential cation channel subfamily V member, TRPV4 that is known to act as a mechanosensor in wide variaty of tissues and control ion-influx in a spatio-temporal way. Here we report that TRPV4 is prominently expressed in the stem/progenitor cell populations of the mammary epithelium and seems important for the lineage-specific differentiation, consequently affecting mechanical features of the mature mammary epithelium. This was evident by the lack of several markers for mature myoepithelial and luminal epithelial cells in TRPV4-depleted cell lines. Interestingly, TRPV4 expression is controlled in a tension-dependent manner and it also impacts differentation process dependently on the stiffness of the microenvironment. Furthermore, such cells in a 3D compartment were disabled to maintain normal mammosphere structures and displayed abnormal lumen formation, size of the structures and disrupted cellular junctions. Mechanosensitive TRPV4 channel therefore act as critical player in the homeostasis of normal mammary epithelium through sensing the physical environment and guiding accordingly differentiation and structural organization of the bilayered mammary epithelium.https://doi.org/10.1038/s41598-024-57346-xTRPV4MechanosensingMammary epitheliumDifferentiationBreast cancerActin cytoskeleton |
| spellingShingle | Kärki Tytti Koskimäki Sanna Guenther Carla Pirhonen Jonatan Rajakylä Kaisa Tojkander Sari Mechanosensitive TRPV4 channel guides maturation and organization of the bilayered mammary epithelium Scientific Reports TRPV4 Mechanosensing Mammary epithelium Differentiation Breast cancer Actin cytoskeleton |
| title | Mechanosensitive TRPV4 channel guides maturation and organization of the bilayered mammary epithelium |
| title_full | Mechanosensitive TRPV4 channel guides maturation and organization of the bilayered mammary epithelium |
| title_fullStr | Mechanosensitive TRPV4 channel guides maturation and organization of the bilayered mammary epithelium |
| title_full_unstemmed | Mechanosensitive TRPV4 channel guides maturation and organization of the bilayered mammary epithelium |
| title_short | Mechanosensitive TRPV4 channel guides maturation and organization of the bilayered mammary epithelium |
| title_sort | mechanosensitive trpv4 channel guides maturation and organization of the bilayered mammary epithelium |
| topic | TRPV4 Mechanosensing Mammary epithelium Differentiation Breast cancer Actin cytoskeleton |
| url | https://doi.org/10.1038/s41598-024-57346-x |
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