# Mucosal Repair in Gut Surgical Disorders

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $494,809

## Abstract

Abstract
 Acute injury of the gut mucosa occurs commonly in patients with critical surgical
events such as trauma, thermal injury, shock, and massive surgical operations.
Because the exact mechanisms underlying gut mucosal injury/repair remain largely
unknown, effective therapies to preserve the epithelial integrity in patients with critical
surgical illness are limited, leading to acute massive hemorrhage, epithelial barrier
dysfunction, sepsis, and in some instances multiple organ dysfunction syndrome and
death. Recently, circular RNAs (circRNAs) have drawn increasing interest due to their
prevalence and range of potential biological functions by interacting with microRNAs
(miRNAs) and RNA-binding proteins (RBPs). In preliminary studies, our genome-wide
circRNA expression profiles reveal that ~300 circRNAs from total 9360, including Cdr1as
and circHIPK3, which were differentially expressed between injured mucosa induced by
septic stress vs uninjured mucosa from control mice. Ectopically expressed Cdr1as
inhibited intestinal epithelial repair after wounding, whereas circHIPK3 promoted
intestinal epithelial regeneration. Cdr1as and circHIPK3 were also found to interact with
several miRNAs such as miR-7 and miR-29b. Based on these exciting observations, we
advance a paradigm-shifting hypothesis that circRNAs Cdr1as and circHIPK3 play an
important role in intestinal mucosal repair by interacting with given miRNAs after acute
injury under critical surgical conditions. Three specific aims are proposed to test the
hypothesis: 1) To define the exact roles of Cdr1as and circHIPK3 in the regulation of
intestinal mucosal repair after acute injury induced by surgical stress; 2) To identify novel
target miRNAs of Cdr1as and circHIPK3 that are important for intestinal mucosal repair
after acute injury; and 3) To characterize the mechanism by which cellular abundances
of Cdr1as and circHIPK3 are regulated in response to critical surgical stress.
Completion of these experiments will make a significant conceptual advance by linking
the circRNA/miRNA interaction with gut mucosal repair after acute injury in patients with
critical surgical illnesses. The unique cellular stability and capacity of circRNAs to
interact with miRNAs and RBPs will also place circRNAs as promising targets or as
therapeutic vectors for developing new treatment to maintain gut epithelial integrity
or/and enhance mucosal repair after injury in surgical clinical setting.

## Key facts

- **NIH application ID:** 10017192
- **Project number:** 5R01DK061972-17
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Jian-Ying Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $494,809
- **Award type:** 5
- **Project period:** 2002-07-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017192

## Citation

> US National Institutes of Health, RePORTER application 10017192, Mucosal Repair in Gut Surgical Disorders (5R01DK061972-17). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10017192. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*