Keratinocyte Integrin α3β1 Promotes Efficient Healing of Wound Epidermis
To date, studies of the role for epidermal integrin α3β1 in cutaneous wound re-epithelialization have produced conflicting results: wound studies in skin from global α3-null neonatal mice have implicated the integrin in promoting timely wound re-epithelialization, whereas studies in adult mice with...
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Elsevier
2025-01-01
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| Series: | JID Innovations |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026724000572 |
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| author | Sanjana Dhulipalla Giesse Albeche Duarte Lei Wu Mathieu R. DiPersio John M. Lamar C. Michael DiPersio Whitney M. Longmate |
| author_facet | Sanjana Dhulipalla Giesse Albeche Duarte Lei Wu Mathieu R. DiPersio John M. Lamar C. Michael DiPersio Whitney M. Longmate |
| author_sort | Sanjana Dhulipalla |
| collection | DOAJ |
| description | To date, studies of the role for epidermal integrin α3β1 in cutaneous wound re-epithelialization have produced conflicting results: wound studies in skin from global α3-null neonatal mice have implicated the integrin in promoting timely wound re-epithelialization, whereas studies in adult mice with constitutive, epidermal-specific α3β1 deletion have not. The objective of this study was to utilize a model of inducible α3β1 deletion in the epidermis to clarify the role of α3β1 in the healing of adult wounds. We utilized the recently developed transgenic K14Cre-ERT::α3flx/flx mice (ie, inducible α3 epidermal knockout), permitting us to delete floxed Itga3 alleles (α3flx/flx) from epidermis just prior to wounding with topical treatment of 4-hydroxytamoxifen. This allows for the elucidation of α3β1-dependent wound healing in adult skin, free from compensatory mechanisms that may occur after embryonic deletion of epidermal α3β1 in the widely used constitutive α3β1-knockout mouse. We found that re-epithelializing wound gaps are larger in inducible α3 epidermal knockout mice than in control mice, indicating delayed healing, and that epidermal integrin α3β1 promotes healing of wounds, at least in part by enhancing keratinocyte proliferation. This work provides essential rationale for future studies to investigate integrin α3β1 as a therapeutic target to facilitate wound healing. |
| format | Article |
| id | doaj-art-9b04932c2df54f0cbac04e4ba2a19c8b |
| institution | Kabale University |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JID Innovations |
| spelling | doaj-art-9b04932c2df54f0cbac04e4ba2a19c8b2025-01-11T06:42:09ZengElsevierJID Innovations2667-02672025-01-0151100310Keratinocyte Integrin α3β1 Promotes Efficient Healing of Wound EpidermisSanjana Dhulipalla0Giesse Albeche Duarte1Lei Wu2Mathieu R. DiPersio3John M. Lamar4C. Michael DiPersio5Whitney M. Longmate6Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USADepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USADepartment of Surgery, Albany Medical College, Albany, New York, USADepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USADepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USADepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA; Department of Surgery, Albany Medical College, Albany, New York, USADepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA; Department of Surgery, Albany Medical College, Albany, New York, USA; Correspondence: Whitney M. Longmate, Albany Medical College, Mail Code 8, Room MR-424, 47 New Scotland Avenue, Albany, New York 12208-3479, USA.To date, studies of the role for epidermal integrin α3β1 in cutaneous wound re-epithelialization have produced conflicting results: wound studies in skin from global α3-null neonatal mice have implicated the integrin in promoting timely wound re-epithelialization, whereas studies in adult mice with constitutive, epidermal-specific α3β1 deletion have not. The objective of this study was to utilize a model of inducible α3β1 deletion in the epidermis to clarify the role of α3β1 in the healing of adult wounds. We utilized the recently developed transgenic K14Cre-ERT::α3flx/flx mice (ie, inducible α3 epidermal knockout), permitting us to delete floxed Itga3 alleles (α3flx/flx) from epidermis just prior to wounding with topical treatment of 4-hydroxytamoxifen. This allows for the elucidation of α3β1-dependent wound healing in adult skin, free from compensatory mechanisms that may occur after embryonic deletion of epidermal α3β1 in the widely used constitutive α3β1-knockout mouse. We found that re-epithelializing wound gaps are larger in inducible α3 epidermal knockout mice than in control mice, indicating delayed healing, and that epidermal integrin α3β1 promotes healing of wounds, at least in part by enhancing keratinocyte proliferation. This work provides essential rationale for future studies to investigate integrin α3β1 as a therapeutic target to facilitate wound healing.http://www.sciencedirect.com/science/article/pii/S2667026724000572IntegrinKeratinocyteProliferationRe-epithelializationWound healing |
| spellingShingle | Sanjana Dhulipalla Giesse Albeche Duarte Lei Wu Mathieu R. DiPersio John M. Lamar C. Michael DiPersio Whitney M. Longmate Keratinocyte Integrin α3β1 Promotes Efficient Healing of Wound Epidermis JID Innovations Integrin Keratinocyte Proliferation Re-epithelialization Wound healing |
| title | Keratinocyte Integrin α3β1 Promotes Efficient Healing of Wound Epidermis |
| title_full | Keratinocyte Integrin α3β1 Promotes Efficient Healing of Wound Epidermis |
| title_fullStr | Keratinocyte Integrin α3β1 Promotes Efficient Healing of Wound Epidermis |
| title_full_unstemmed | Keratinocyte Integrin α3β1 Promotes Efficient Healing of Wound Epidermis |
| title_short | Keratinocyte Integrin α3β1 Promotes Efficient Healing of Wound Epidermis |
| title_sort | keratinocyte integrin α3β1 promotes efficient healing of wound epidermis |
| topic | Integrin Keratinocyte Proliferation Re-epithelialization Wound healing |
| url | http://www.sciencedirect.com/science/article/pii/S2667026724000572 |
| work_keys_str_mv | AT sanjanadhulipalla keratinocyteintegrina3b1promotesefficienthealingofwoundepidermis AT giessealbecheduarte keratinocyteintegrina3b1promotesefficienthealingofwoundepidermis AT leiwu keratinocyteintegrina3b1promotesefficienthealingofwoundepidermis AT mathieurdipersio keratinocyteintegrina3b1promotesefficienthealingofwoundepidermis AT johnmlamar keratinocyteintegrina3b1promotesefficienthealingofwoundepidermis AT cmichaeldipersio keratinocyteintegrina3b1promotesefficienthealingofwoundepidermis AT whitneymlongmate keratinocyteintegrina3b1promotesefficienthealingofwoundepidermis |