# Posttranscriptional Control of Gut Mucosal Defense and Homeostasis

> **NIH VA I01** · BALTIMORE VA MEDICAL CENTER · 2024 · —

## Abstract

Gut mucosal injury occurs commonly in patients with inflammatory bowel disease (IBD)
and critical surgical disorders such as trauma, massive thermal injuries, sepsis, and emergent
surgical operations. Effective therapies to preserve the integrity of the intestinal epithelium and
enhance recovery of damaged mucosa in patients with critical illnesses are limited; because of
poorly understood mechanisms underlying gut mucosal injury and repair. Achieving a better
understanding of the pathogenesis of mucosal injury/erosions and developing effective therapies
to protect the epithelium from injury and promote repair after wounding in patients with critical
illness are still urgent challenges. Long noncoding RNAs (lncRNAs) regulate a variety of
biological functions and are intimately involved in the pathogenesis of diverse human diseases.
Although emerging evidence increasingly points to the importance of lncRNAs in maintaining gut
epithelial integrity, their exact roles in the mechanisms regulating intestinal mucosal repair after
injury remain largely unknown.
 Recent studies also reveal that mitochondrial metabolism is essential for maintaining
intestinal epithelial integrity, while targeted deletion of mitochondrial prohibitin-1 and Hsp60
causes murine ileitis. By using genome-wide profile analysis, we identified hundreds of
lncRNAs, including uc.230 and growth arrest specific 5 (GAS5), which are differentially
expressed in the intestinal mucosa in response to pathological stress. Our preliminary studies
indicate that a) after wounding, ulcerative colitis (uc).230 is required for intestinal mucosal repair
whereas GAS5 induction delays epithelial recovery; and b) silencing uc.230 or overexpressing
GAS5 results in mitochondrial dysfunction in intestinal epithelial cells. Based on our exciting
observations, we HYPOTHESIZE that uc.230 and GAS5 regulate intestinal mucosal repair after
injury by altering mitochondrial function. Three specific aims are designed to test this
hypothesis: 1) to define the exact roles of uc.230 and GAS5 in regulating intestinal mucosal
repair after injury in critical pathological conditions; 2) to determine whether uc.230 and GAS5
modulate injury-induced intestinal mucosal regeneration by altering mitochondrial metabolism;
and 3) to define the mechanisms whereby cellular levels of uc.230 and GAS5 are regulated in
response to pathological stress. Completion of these specific aims will provide a substantial
conceptual advance by linking lncRNA-mediated changes in mitochondrial metabolism with
injury-induced regeneration of the intestinal epithelium and will create a fundamental basis for
developing novel therapies to preserve intestinal epithelial integrity and enhance mucosal repair
in the clinical setting for Veterans with critical illnesses.

## Key facts

- **NIH application ID:** 10697493
- **Project number:** 2I01BX000332-13
- **Recipient organization:** BALTIMORE VA MEDICAL CENTER
- **Principal Investigator:** Jian-Ying Wang
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2009-04-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10697493

## Citation

> US National Institutes of Health, RePORTER application 10697493, Posttranscriptional Control of Gut Mucosal Defense and Homeostasis (2I01BX000332-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10697493. Licensed CC0.

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