Activation of mechanoreceptor Piezo1 inhibits enteric neuronal growth and migration in vitro
IntroductionDysfunction of the enteric nervous system (ENS) is linked to a myriad of gastrointestinal (GI) disorders. Piezo1 is a mechanosensitive ion channel found throughout the GI tract, but its role in the ENS is largely unknown. We hypothesize that Piezo1 plays an important role in the growth a...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Molecular Neuroscience |
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| author | Chioma Moneme Oluyinka O. Olutoye Michał F. Sobstel Yuwen Zhang Xinyu Zhou Jacob L. Kaminer Britney A. Hsu Chengli Shen Arabinda Mandal Hui Li Hui Li Ling Yu Ling Yu Swathi Balaji Swathi Balaji Sundeep G. Keswani Sundeep G. Keswani Lily S. Cheng Lily S. Cheng Lily S. Cheng |
| author_facet | Chioma Moneme Oluyinka O. Olutoye Michał F. Sobstel Yuwen Zhang Xinyu Zhou Jacob L. Kaminer Britney A. Hsu Chengli Shen Arabinda Mandal Hui Li Hui Li Ling Yu Ling Yu Swathi Balaji Swathi Balaji Sundeep G. Keswani Sundeep G. Keswani Lily S. Cheng Lily S. Cheng Lily S. Cheng |
| author_sort | Chioma Moneme |
| collection | DOAJ |
| description | IntroductionDysfunction of the enteric nervous system (ENS) is linked to a myriad of gastrointestinal (GI) disorders. Piezo1 is a mechanosensitive ion channel found throughout the GI tract, but its role in the ENS is largely unknown. We hypothesize that Piezo1 plays an important role in the growth and development of the ENS.MethodsEnteric neural crest-derived progenitor cells (ENPC) were isolated from adult mouse intestine and propagated in culture as neurospheres. ENPC-derived neurons were then subject to in vitro stretch in the presence or absence of Piezo1 antagonist (GsMTx4). Transcriptomes of stretched and unstretched ENPC-derived cells were compared using bulk RNA sequencing. Enteric neurons were also cultured under static conditions in the presence of Piezo1 agonist (Yoda1) or antagonist. Neuronal phenotype, migration, and recovery from injury were compared between groups.ResultsThough stretch did not cause upregulation of Piezo1 expression in enteric neurons, both stretch and Piezo1 activation produced similar alterations in neuronal morphology. Compared to control, neurite length was significantly shorter when stretched and in the presence of Piezo1 activation. Piezo1 inhibition prevented a significant reduction in neurite length in stretched neurons. Piezo1 inhibition also led to significantly increased neuronal migration, whereas Piezo1 activation resulted in significantly decreased neuronal migration and slower neuronal recovery from injury.ConclusionMechanotransduction plays an important role in regulating normal GI function. Our results suggest that the Piezo1 mechanoreceptor may play an important role in the ENS as its activation leads to decreased neuronal growth and migration. Piezo1 could be an important target for diseases of ENS dysfunction and development. |
| format | Article |
| id | doaj-art-a5a52d4c095149c3bfe1390676aa8564 |
| institution | OA Journals |
| issn | 1662-5099 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj-art-a5a52d4c095149c3bfe1390676aa85642025-08-20T02:34:36ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992024-12-011710.3389/fnmol.2024.14740251474025Activation of mechanoreceptor Piezo1 inhibits enteric neuronal growth and migration in vitroChioma Moneme0Oluyinka O. Olutoye1Michał F. Sobstel2Yuwen Zhang3Xinyu Zhou4Jacob L. Kaminer5Britney A. Hsu6Chengli Shen7Arabinda Mandal8Hui Li9Hui Li10Ling Yu11Ling Yu12Swathi Balaji13Swathi Balaji14Sundeep G. Keswani15Sundeep G. Keswani16Lily S. Cheng17Lily S. Cheng18Lily S. Cheng19Department of Surgery, University of Virginia, Charlottesville, VA, United StatesDepartment of Surgery, Baylor College of Medicine, Houston, TX, United StatesDepartment of Surgery, University of Virginia, Charlottesville, VA, United StatesDepartment of Surgery, University of Virginia, Charlottesville, VA, United StatesDepartment of Surgery, University of Virginia, Charlottesville, VA, United StatesDepartment of Surgery, University of Virginia, Charlottesville, VA, United StatesDepartment of Pediatric Surgery, Texas Children's Hospital, Houston, TX, United StatesDepartment of Surgery, University of Virginia, Charlottesville, VA, United StatesDepartment of Surgery, University of Virginia, Charlottesville, VA, United StatesDepartment of Surgery, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pediatric Surgery, Texas Children's Hospital, Houston, TX, United StatesDepartment of Surgery, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pediatric Surgery, Texas Children's Hospital, Houston, TX, United StatesDepartment of Surgery, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pediatric Surgery, Texas Children's Hospital, Houston, TX, United StatesDepartment of Surgery, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pediatric Surgery, Texas Children's Hospital, Houston, TX, United StatesDepartment of Surgery, University of Virginia, Charlottesville, VA, United StatesDepartment of Surgery, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pediatric Surgery, Texas Children's Hospital, Houston, TX, United StatesIntroductionDysfunction of the enteric nervous system (ENS) is linked to a myriad of gastrointestinal (GI) disorders. Piezo1 is a mechanosensitive ion channel found throughout the GI tract, but its role in the ENS is largely unknown. We hypothesize that Piezo1 plays an important role in the growth and development of the ENS.MethodsEnteric neural crest-derived progenitor cells (ENPC) were isolated from adult mouse intestine and propagated in culture as neurospheres. ENPC-derived neurons were then subject to in vitro stretch in the presence or absence of Piezo1 antagonist (GsMTx4). Transcriptomes of stretched and unstretched ENPC-derived cells were compared using bulk RNA sequencing. Enteric neurons were also cultured under static conditions in the presence of Piezo1 agonist (Yoda1) or antagonist. Neuronal phenotype, migration, and recovery from injury were compared between groups.ResultsThough stretch did not cause upregulation of Piezo1 expression in enteric neurons, both stretch and Piezo1 activation produced similar alterations in neuronal morphology. Compared to control, neurite length was significantly shorter when stretched and in the presence of Piezo1 activation. Piezo1 inhibition prevented a significant reduction in neurite length in stretched neurons. Piezo1 inhibition also led to significantly increased neuronal migration, whereas Piezo1 activation resulted in significantly decreased neuronal migration and slower neuronal recovery from injury.ConclusionMechanotransduction plays an important role in regulating normal GI function. Our results suggest that the Piezo1 mechanoreceptor may play an important role in the ENS as its activation leads to decreased neuronal growth and migration. Piezo1 could be an important target for diseases of ENS dysfunction and development.https://www.frontiersin.org/articles/10.3389/fnmol.2024.1474025/fullenteric nervous system (ENS)enteric neural crest-derived progenitor cells (ENPC)biomechanical forcemechanotransductionneuronal cell migrationneuronal regeneration |
| spellingShingle | Chioma Moneme Oluyinka O. Olutoye Michał F. Sobstel Yuwen Zhang Xinyu Zhou Jacob L. Kaminer Britney A. Hsu Chengli Shen Arabinda Mandal Hui Li Hui Li Ling Yu Ling Yu Swathi Balaji Swathi Balaji Sundeep G. Keswani Sundeep G. Keswani Lily S. Cheng Lily S. Cheng Lily S. Cheng Activation of mechanoreceptor Piezo1 inhibits enteric neuronal growth and migration in vitro Frontiers in Molecular Neuroscience enteric nervous system (ENS) enteric neural crest-derived progenitor cells (ENPC) biomechanical force mechanotransduction neuronal cell migration neuronal regeneration |
| title | Activation of mechanoreceptor Piezo1 inhibits enteric neuronal growth and migration in vitro |
| title_full | Activation of mechanoreceptor Piezo1 inhibits enteric neuronal growth and migration in vitro |
| title_fullStr | Activation of mechanoreceptor Piezo1 inhibits enteric neuronal growth and migration in vitro |
| title_full_unstemmed | Activation of mechanoreceptor Piezo1 inhibits enteric neuronal growth and migration in vitro |
| title_short | Activation of mechanoreceptor Piezo1 inhibits enteric neuronal growth and migration in vitro |
| title_sort | activation of mechanoreceptor piezo1 inhibits enteric neuronal growth and migration in vitro |
| topic | enteric nervous system (ENS) enteric neural crest-derived progenitor cells (ENPC) biomechanical force mechanotransduction neuronal cell migration neuronal regeneration |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2024.1474025/full |
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