TRPV4 Plays a Role in Matrix Stiffness-Induced Macrophage Polarization
Phenotypic polarization of macrophages is deemed essential in innate immunity and various pathophysiological conditions. We have now determined key aspects of the molecular mechanism by which mechanical cues regulate macrophage polarization. We show that Transient Receptor Potential Vanilloid 4 (TRP...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-12-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.570195/full |
| _version_ | 1819061803293868032 |
|---|---|
| author | Bidisha Dutta Rishov Goswami Shaik O. Rahaman |
| author_facet | Bidisha Dutta Rishov Goswami Shaik O. Rahaman |
| author_sort | Bidisha Dutta |
| collection | DOAJ |
| description | Phenotypic polarization of macrophages is deemed essential in innate immunity and various pathophysiological conditions. We have now determined key aspects of the molecular mechanism by which mechanical cues regulate macrophage polarization. We show that Transient Receptor Potential Vanilloid 4 (TRPV4), a mechanosensitive ion channel, mediates substrate stiffness-induced macrophage polarization. Using atomic force microscopy, we showed that genetic ablation of TRPV4 function abrogated fibrosis-induced matrix stiffness generation in skin tissues. We have determined that stiffer skin tissue promotes the M1 macrophage subtype in a TRPV4-dependent manner; soft tissue does not. These findings were further validated by our in vitro results which showed that stiff matrix (50 kPa) alone increased expression of macrophage M1 markers in a TRPV4-dependent manner, and this response was further augmented by the addition of soluble factors; neither of which occurred with soft matrix (1 kPa). A direct requirement for TRPV4 in M1 macrophage polarization spectrum in response to increased stiffness was evident from results of gain-of-function assays, where reintroduction of TRPV4 significantly upregulated the expression of M1 markers in TRPV4 KO macrophages. Together, these data provide new insights regarding the role of TRPV4 in matrix stiffness-induced macrophage polarization spectrum that may be explored in tissue engineering and regenerative medicine and targeted therapeutics. |
| first_indexed | 2024-12-21T14:48:41Z |
| format | Article |
| id | doaj.art-d43d70f40a42405694ef133d36d697b5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T14:48:41Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d43d70f40a42405694ef133d36d697b52022-12-21T18:59:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-12-011110.3389/fimmu.2020.570195570195TRPV4 Plays a Role in Matrix Stiffness-Induced Macrophage PolarizationBidisha DuttaRishov GoswamiShaik O. RahamanPhenotypic polarization of macrophages is deemed essential in innate immunity and various pathophysiological conditions. We have now determined key aspects of the molecular mechanism by which mechanical cues regulate macrophage polarization. We show that Transient Receptor Potential Vanilloid 4 (TRPV4), a mechanosensitive ion channel, mediates substrate stiffness-induced macrophage polarization. Using atomic force microscopy, we showed that genetic ablation of TRPV4 function abrogated fibrosis-induced matrix stiffness generation in skin tissues. We have determined that stiffer skin tissue promotes the M1 macrophage subtype in a TRPV4-dependent manner; soft tissue does not. These findings were further validated by our in vitro results which showed that stiff matrix (50 kPa) alone increased expression of macrophage M1 markers in a TRPV4-dependent manner, and this response was further augmented by the addition of soluble factors; neither of which occurred with soft matrix (1 kPa). A direct requirement for TRPV4 in M1 macrophage polarization spectrum in response to increased stiffness was evident from results of gain-of-function assays, where reintroduction of TRPV4 significantly upregulated the expression of M1 markers in TRPV4 KO macrophages. Together, these data provide new insights regarding the role of TRPV4 in matrix stiffness-induced macrophage polarization spectrum that may be explored in tissue engineering and regenerative medicine and targeted therapeutics.https://www.frontiersin.org/articles/10.3389/fimmu.2020.570195/fullmacrophageTRPV4 agonistmatrix stiffnesspolarizationinflammation |
| spellingShingle | Bidisha Dutta Rishov Goswami Shaik O. Rahaman TRPV4 Plays a Role in Matrix Stiffness-Induced Macrophage Polarization Frontiers in Immunology macrophage TRPV4 agonist matrix stiffness polarization inflammation |
| title | TRPV4 Plays a Role in Matrix Stiffness-Induced Macrophage Polarization |
| title_full | TRPV4 Plays a Role in Matrix Stiffness-Induced Macrophage Polarization |
| title_fullStr | TRPV4 Plays a Role in Matrix Stiffness-Induced Macrophage Polarization |
| title_full_unstemmed | TRPV4 Plays a Role in Matrix Stiffness-Induced Macrophage Polarization |
| title_short | TRPV4 Plays a Role in Matrix Stiffness-Induced Macrophage Polarization |
| title_sort | trpv4 plays a role in matrix stiffness induced macrophage polarization |
| topic | macrophage TRPV4 agonist matrix stiffness polarization inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.570195/full |
| work_keys_str_mv | AT bidishadutta trpv4playsaroleinmatrixstiffnessinducedmacrophagepolarization AT rishovgoswami trpv4playsaroleinmatrixstiffnessinducedmacrophagepolarization AT shaikorahaman trpv4playsaroleinmatrixstiffnessinducedmacrophagepolarization |