# Regulation of Intestinal Epithelial Cell Proliferation

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $424,627

## Abstract

PROJECT SUMMARY/ABSTRACT
The mammalian intestinal epithelium is a continuously renewing and highly regenerative tissue in which
numerous biological processes such as proliferation, differentiation, migration, and apoptosis are carefully
choreographed to achieve homeostasis. Studies have indicated that multiple signaling pathways including the
WNT, NOTCH, BMP and HH form important components of the regulatory network and converge upon the
intestinal crypts where intestinal stem cells (ISCs) reside. Recent studies have identified distinct populations of
ISCs based on the markers that they express. At the present time ISCs are divided into two relatively broad
functional groups: active ISCs (aISCs), a population of crypt base columnar (CBC) cells expressing LGR5,
function as the multipotent stem cells during homeostasis, and quiescent or reserve ISCs (qISCs or rISCs),
which express various markers such as BMI1, LRIG1, mTERT, HOPX, and DCLK1, are slow-cycling during
homeostasis but serve as a source of regeneration following depletion of aISCs due to injury. Despite these
advances significant gaps remain with regard to how extracellular milieu influence behavior of ISCs and how
plasticity of ISCs at physiologic and pathophysiological states is mediated intracellularly. Understanding the
mechanisms that control proliferation and regeneration of intestinal epithelia cells (IECs) will advance the
knowledge of disease processes and therapeutic options for conditions such as cancer and inflammatory bowel
disease. The LONG-TERM GOAL of this renewal application is to understand the molecular mechanisms
regulating intestinal epithelial cell proliferation in physiologic and pathophysiological conditions. The
project supported by grant DK052230 established that the zinc finger transcription factor, Krüppel-like factor 5
(KLF5), plays an important role in regulating proliferation of LGR5-expressing aISCs. Preliminary studies also
show that a related Krüppel-like factor, KLF4, normally expressed in post-mitotic or quiescent IECs, including
BMI1-expressing cells, becomes activated after γ radiation-induced stem cell injury and is in part responsible for
the regenerative response of the intestinal epithelium following irradiation. Based on these observations we
propose the CENTRAL HYPOTHESIS that KLF4 and KLF5 are critical intracellular mediators of the
proliferative, regenerative response of the intestinal epithelium following injury. We propose three
SPECIFIC AIMS to test the hypothesis: (SA1) To investigate the role of KLF4 in modulating the regenerative
response of the intestinal epithelium following γ radiation-induced gut injury; (SA2) To investigate the role of
KLF5 in modulating the regenerative response of the intestinal epithelium after depletion of aISCs; and (SA3) To
establish the mechanism by which KLF4 and KLF5 coordinate with each other to regulate the regenerative
process. These experiments will lead to definitive information on how KLF4 and KLF5 r...

## Key facts

- **NIH application ID:** 10127622
- **Project number:** 5R01DK052230-23
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Vincent W Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $424,627
- **Award type:** 5
- **Project period:** 1997-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127622

## Citation

> US National Institutes of Health, RePORTER application 10127622, Regulation of Intestinal Epithelial Cell Proliferation (5R01DK052230-23). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10127622. Licensed CC0.

---

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