Topical JAG1, a Notch Activator, Accelerates Splinted Cutaneous Excisional Wound Closure in K14-Notch2 Knockout Mice
Abstract
INTRODUCTION: Over 6.5M patients suffer from wound-related complications annually in the USA resulting in a cost of >$25B/yr. Our laboratory is interested in improving the wound healing process. We have previously shown that... [ view full abstract ]
INTRODUCTION: Over 6.5M patients suffer from wound-related complications annually in the USA resulting in a cost of >$25B/yr. Our laboratory is interested in improving the wound healing process. We have previously shown that inhibition of Notch decreases wound healing and that upregulation of Notch increases the rate of wound healing. JAG1 is a known activator of Notch. We hypothesized that topical JAG1 applied to wounds of keratinocyte-specific Notch2 knockout mice would upregulate Notch1 and/or Notch3 resulting in an increased rate of wound healing.
METHODS: K14-Notch2 knockout mice were anesthetized, and two 1cm2 full-thickness wounds were created on their backs. A stent was secured around each wound. Sterile dressings were applied. Dressings were changed every other day after topical application onto the open wound bed of JAG1 (10 nM) or vehicle (PBS). Digital photographs were taken and analyzed using ImageJ. Wound closure was defined by visualization of resurfacing epithelia. Statistical significance was defined as p<0.05.
RESULTS: Wound sizes were similar in both groups at the beginning of treatment. K14-Notch2 knockout mice treated with JAG1 had an increased rate of wound closure when compared to controls.
CONCLUSIONS: JAG1 increased the rate of re-epithelialization of cutaneous wounds in an in vivo stented wound-healing model in K14-Notch2 knockout mice, indicating that Notch signaling plays a crucial role in wound healing. Further studies should evaluate the mechanisms by which Notch2 regulates wound healing. This could result in the development of new therapeutics for wound healing in patients.
Authors
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Kayla Leibl
(University of Wisconsin - Madison)
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Zviadi Aburjania
(University of Alabama - Birmingham)
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Benjamin Giertych
(University of Wisconsin - Madison)
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Timothy King
(University of Alabama at Birmingham)
Topic Areas
Trauma / Critical Care , Other
Session
QS-TCC/CT » Quick-Shot Presentations: Trauma/Critical Care/Acute Care Surgery/Cardiothoracic Surgery (15:00 - Thursday, 21st September, Dearth Tower Conf 2)