Related Experiment Video
Updated: Jan 27, 2026
05:01
A Pathway Association Study Tool for GWAS Analyses of Metabolic Pathway Information
Published on: July 1, 2020
3.7K
STAT3 signalling pathway is implicated in keloid pathogenesis by preliminary transcriptome and open chromatin
Yun-Shain Lee1,2, Ya-Chen Liang2,3, Ping Wu3
1The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, California.
Experimental Dermatology
|March 28, 2019
Summary
Keloid fibroblasts exhibit altered gene expression and epigenetic activity, particularly involving STAT3 signaling. Inhibiting STAT3 shows potential in managing keloid scar formation.
Area of Science:
- Dermatology
- Molecular Biology
- Epigenetics
Background:
- Keloids are complex, tumor-like skin scars resulting from abnormal wound healing.
- The precise molecular mechanisms driving keloid pathogenesis remain poorly understood.
Purpose of the Study:
- To investigate the dynamic epigenetic and transcriptome changes in keloid fibroblasts.
- To explore the role of specific signaling pathways, such as STAT3, in keloid formation.
Main Methods:
- RNA-sequencing (RNA-seq) and ATAC-sequencing (ATAC-seq) on keloid and normal fibroblasts.
- Utilized a humanized keloid mouse model with plasma clot-based skin equivalents.
- Immunohistochemistry and pharmacological inhibition (cucurbitacin I) to assess pathway involvement.
Main Results:
- RNA-seq identified enriched gene ontology terms related to fibrosis, Wnt-β-catenin, TGF-β, and epithelial-mesenchymal transition (EMT).
- ATAC-seq highlighted STAT3 signaling as the most significantly enriched pathway in keloid fibroblasts, followed by Wnt and EMT pathways.
- Activated STAT3 (phospho-STAT3 Tyr705) and upregulated β-catenin were confirmed in keloid tissues and the mouse model.
- STAT3 inhibition demonstrated a dose-dependent effect on collagen type I expression in keloid skin equivalents.
Conclusions:
- STAT3 signaling plays a significant role in keloid pathogenesis.
- The humanized keloid mouse model is a valuable tool for studying keloid formation mechanisms.
- Findings suggest potential therapeutic targets for keloid treatment by modulating STAT3 activity.
Related Concept Videos
01:19Interactions Between Signaling Pathways
7.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.3K
03:14Notch Signaling Pathway
6.5K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.5K
02:33Hedgehog Signaling Pathway
9.9K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
9.9K
01:28Insulin: The Receptor and Signaling Pathways
2.9K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
2.9K
01:11IP3/DAG Signaling Pathway
14.4K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
14.4K
01:28Nitric Oxide Signaling Pathway
6.2K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
6.2K