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Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.
Published on: March 25, 2020
Role of TGF beta-mediated inflammation in cutaneous wound healing
Xiao-Jing Wang1, Gangwen Han, Philip Owens
1Department of Otolaryngology, Oregon Health & Science University, Portland, Oregon 97239, USA. wangxiao@ohsu.edu
Abstract:
Among many molecules known to influence wound healing, transforming growth factor beta 1 (TGF beta 1) has the broadest spectrum of actions, affecting all cell types that are involved in all stages of wound healing. Both positive and negative effects of TGF beta 1 on wound healing have been reported. However, the underlying mechanisms are largely unknown. We observed that endogenous TGF beta 1 was elevated in a narrow window of time after injury, and transgenic mice constitutively overexpressing wild-type TGF beta 1 in keratinocytes (K5.TGF beta 1wt) exhibited a significant delay in full-thickness wound healing as compared to non-transgenic mice. Delayed wound healing was associated with profound inflammation throughout all stages of wound healing in K5.TGF beta 1wt mice. Our data suggest that excessive and prolonged TGF beta 1 at the wound site does not benefit wound healing, which is partially owing to its pro-inflammatory effect. Future studies need to be conducted to assess whether tightly regulated TGF beta 1 expression will benefit wound healing. To this end, we have developed a gene-switch TGF beta 1 transgenic system that allows TGF beta 1 induction in keratinocytes temporally with desired levels. These mice will provide a tool to study stage-specific effects of TGF beta 1 on cutaneous wound healing.
Insights
Excessive transforming growth factor beta 1 (TGF-β1) delays wound healing by increasing inflammation. Tightly regulated TGF-β1 expression may improve healing outcomes, necessitating further research.
Area of Science:
- Wound healing research
- Molecular biology
- Dermatology
Background:
- Transforming growth factor beta 1 (TGF-β1) influences all stages of wound healing.
- Both beneficial and detrimental effects of TGF-β1 on wound healing have been documented.
- Mechanisms underlying TGF-β1's role in wound healing remain unclear.
Purpose of the Study:
- To investigate the impact of constitutive and tightly regulated transforming growth factor beta 1 (TGF-β1) expression on cutaneous wound healing.
- To elucidate the mechanisms behind TGF-β1's dual effects on wound repair.
Main Methods:
- Utilized transgenic mice overexpressing wild-type TGF-β1 in keratinocytes (K5.TGF-β1wt).
- Analyzed full-thickness wound healing progression and associated inflammatory responses.
- Developed a gene-switch TGF-β1 transgenic system for temporal and level-controlled induction.
Main Results:
- Constitutive overexpression of TGF-β1 in keratinocytes significantly delayed wound healing in K5.TGF-β1wt mice.
- Delayed healing was characterized by prolonged and profound inflammation.
- Endogenous TGF-β1 levels were transiently elevated post-injury.
Conclusions:
- Excessive and prolonged TGF-β1 at wound sites impairs healing, partly due to pro-inflammatory effects.
- Tightly regulated TGF-β1 expression is crucial for optimal wound healing.
- The novel gene-switch TGF-β1 transgenic system offers a valuable tool for studying stage-specific TGF-β1 functions in skin wound repair.
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