# The role of long non-coding RNA GAS5 in diabetic wounds

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $307,334

## Abstract

Summary
Having reached epidemic proportions in the United States and globally, diabetes and the associated wound
healing impairment is a significant and growing clinical problem. In 2014, more than 70,000 lower extremity
amputations disabled diabetic patients, of which nearly 85% were preceded by a diabetic wound. Despite the
enormous impact of these wounds on both individuals and society, effective therapies are lacking. Thus, the
improving/accelerating the healing of cutaneous wound in diabetics has the potential to significantly improve
patient outcomes and reduce healthcare expenditures. The long-term goal of our research is to develop
therapies to effectively promote healing of diabetic wounds. The defects in wound healing in diabetics is
multifactorial. A central feature of diabetic wounds is the persistence of chronic inflammation, partly due to the
prolonged presence of proinflammatory (M1) macrophages. The presence of the M1 macrophage phenotype
and failure to transition to the regenerative or pro-remodeling (M2) macrophage phenotype have been shown
to play a role in the pathogenesis of the diabetic wounds; however, the mechanism underlying this relationship
remains unclear. Dysregulated expression of long non-coding RNAs (lncRNAs) has recently been implicated in
wound healing, and it is thought that dysregulated expression or function of lncRNAs might contribute to poor
wound healing. The lncRNA, growth arrest specific 5 (GAS5), has been widely studied in numerous human
diseases, although a role in wound healing had not been observed. We recently found evidence that GAS5
does, in fact, play a role in wound healing. Our recent observations reveal abnormal GAS5 levels in impaired
healing of diabetic wounds: 1) The expression of GAS5 is significantly increased in diabetic wounds and in
cells isolated from diabetic wounds when compared to non-diabetic tissues; 2) Hyperglycemia induces GAS5
expression in macrophages in vitro; 3) Overexpression of GAS5 in vitro promotes macrophage polarization
towards an M1 phenotype by upregulating STAT1; 4) GAS5 expression is significantly elevated in undamaged
human diabetic skin relative to non-diabetic skin; and 5) Most importantly, GAS5 loss-of-function enhances
diabetic wound healing. Given the compelling evidence that GAS5 is involved in wound healing, it becomes
essential to determine the mechanisms of GAS5 action. Filling this gap in knowledge holds promise to
overcome a heretofore impenetrable hurdle preventing development of novel therapeutic strategies to address
the rising morbidity associated with diabetic wounds. Our objective here is to elucidate the mechanisms
through which GAS5 impairs diabetic wound healing, and to assess GAS5 as a therapeutic target for improving
diabetic wound healing. Our central hypothesis is that elevated GAS5 expression in diabetic wounds
causes persistence of the M1 macrophage phenotype, increased inflammation, and delayed wound
healing. The rationale for this work ...

## Key facts

- **NIH application ID:** 10137263
- **Project number:** 5R01GM128660-04
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Junwang Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $307,334
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137263

## Citation

> US National Institutes of Health, RePORTER application 10137263, The role of long non-coding RNA GAS5 in diabetic wounds (5R01GM128660-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10137263. Licensed CC0.

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