# Krüppel-like Factors in the Gastrointestinal Tract

**Authors:** Dharmendra Bhargava, Anchal Neha Bhargava, Jonathan P. Katz

PMC · DOI: 10.3390/cells14191513 · 2025-09-28

## TL;DR

This paper reviews how Krüppel-like factors (KLFs) regulate gastrointestinal development, health, and disease through complex interactions with key signaling pathways.

## Contribution

The paper provides a comprehensive review of KLF functions in the GI tract, emphasizing their context-dependent roles and therapeutic potential.

## Key findings

- KLFs regulate GI development by orchestrating gene programming during organogenesis.
- KLFs modulate GI homeostasis, inflammation, and cancer through interactions with pathways like Wnt and NF-κB.
- KLFs show tissue-specific expression and function, making them potential targets for GI diseases.

## Abstract

What are the main findings?
The Krüppel-like factors (KLFs) occupy nodal positions at the intersection of transcriptional regulation, metabolism, stress response, and cell fate determination in both normal gastrointestinal (GI) physiology and diseaseThe functions of the KLFs within the GI tract are highly context-dependent.

The Krüppel-like factors (KLFs) occupy nodal positions at the intersection of transcriptional regulation, metabolism, stress response, and cell fate determination in both normal gastrointestinal (GI) physiology and disease

The functions of the KLFs within the GI tract are highly context-dependent.

What is the implication of the main finding?
Understanding specific KLF functions in the GI tract is essential.The KLFs can potentially be targeted for GI diseases.

Understanding specific KLF functions in the GI tract is essential.

The KLFs can potentially be targeted for GI diseases.

The Krüppel-like factors (KLFs) are a family of transcriptional regulators that play crucial roles in regulating diverse cellular processes including development, proliferation, differentiation, metabolism, and carcinogenesis across various tissues. KLFs play pivotal roles in gastrointestinal pathologies, and exhibit tissue- and cell-type-specific expression patterns throughout the gastrointestinal tract. During gastrointestinal (GI) development, KLFs orchestrate the transition from embryonic to adult gene programming, with specific family members being essential for proper organogenesis and tissue formation. KLFs also function as context-dependent modulators of GI homeostasis, inflammation, and carcinogenesis in adult tissues and interact with major signaling pathways such as PI3K/AKT, NF-κB, Wnt, Notch, MAPK, and TGF-β. This review comprehensively examines the roles of KLFs in GI health and disease, focusing on their expression patterns, regulatory mechanisms, function in normal homeostasis, and therapeutic implications for gastrointestinal disorders.

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}
- **Diseases:** carcinogenesis (MESH:D063646), gastrointestinal disorders (MESH:D005767), inflammation (MESH:D007249)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12523280/full.md

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Source: https://tomesphere.com/paper/PMC12523280