# Role of skin injury-induced inflammation in wound healing

> **NIH VA I01** · RLR VA MEDICAL CENTER · 2021 · —

## Abstract

PROJECT SUMMARY
Chronic skin wounds like diabetic foot ulcers (DFU) are a serious medical problem in Veterans. Up to one third
of patients with diabetes develop DFU, a leading cause of lower leg amputations as well as skin and bone
infections and an independent risk factor for death. As current therapies are limited and often ineffective, there
is a critical need to better understand pathogenesis in order to identify new and improved therapies for chronic
wounds in diabetes and other disease states. Repetitive skin injury and skin inflammation are independently
implicated in DFU pathogenesis; however, gaps in knowledge exist regarding how skin injury and inflammation
interact in diabetic (and healthy) skin and how this interaction could impair wound healing. We recently
identified an inflammatory response that is activated by mechanical skin injury and refer to this as the skin
injury-induced inflammatory response. Our preliminary data suggest the IL-1 signaling initiates this response
and contributes to DFU pathogenesis. The objective of this project is to determine how IL-1 signaling regulates
the skin injury-induced inflammatory response and contributes to normal wound healing as well as impaired
wound healing in a mouse model of type 2 diabetes. Our central hypothesis is IL-1 signaling activates the skin
injury-induced inflammatory response and promotes scarring during normal and diabetic wound healing and
that dysregulated IL-1 signaling amplifies inflammation and impairs diabetic wound healing. Aim 1 will
determine the role of keratinocyte-derived IL-1 and IL-1 receptor signaling during normal skin wound healing in
mice and determine if disrupting IL-1 signaling reduces scarring and enhances normal wound healing. Aim 2
will examine the role of IL-1 and IL-1 receptor signaling in a mouse model of type 2 diabetes mellitus and
determine if disrupting IL-1 signaling enhances diabetic wound healing. Aim 3 will use ex vivo-cultured human
skin from healthy and diabetics subjects to define the contributions of IL-1 and blood sugar control to the skin
injury-induced inflammatory response transcriptome in whole skin tissue and at the level of single cells. This
project will define the role of IL-1/IL-1R1 axis activation on skin injury-induced inflammation in healthy and
diabetic human and mouse skin and the consequences of IL-1/IL-1R1 signaling during wound healing. This
coupled with identification of new molecular targets during these studies will facilitate further research and
development of new therapies to promote wound healing in diabetes and other disease states.

## Key facts

- **NIH application ID:** 10016837
- **Project number:** 1I01CX002141-01
- **Recipient organization:** RLR VA MEDICAL CENTER
- **Principal Investigator:** Matthew J Turner
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016837

## Citation

> US National Institutes of Health, RePORTER application 10016837, Role of skin injury-induced inflammation in wound healing (1I01CX002141-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10016837. Licensed CC0.

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