Related Experiment Video
Updated: Jul 8, 2026
08:20
In Vitro Model of Human Cutaneous Hypertrophic Scarring using Macromolecular Crowding
Published on: May 1, 2020
METTL3-mediated m6A modification stabilizes COL1A1 mRNA to promote extracellular matrix accumulation in keloids
Yanbin Zhai1, Xiaofei Wang2, Wanli Guo1
1Department of Burns (First Ward), Center for Burn, Plastic Surgery and Wound Repair , General Hospital of Taiyuan Iron and Steel (Group) Co., Ltd. (The Sixth Hospital of Shanxi Medical University), Taiyuan, Shanxi, 030009, China.
Experimental Cell Research
|July 6, 2026
Summary
METTL3, an RNA modifier, drives keloid fibrosis by stabilizing COL1A1 mRNA for increased collagen production. Inhibiting METTL3 reduces scar formation, offering a new therapeutic target for pathological scarring.
Area of Science:
- Molecular Biology
- Dermatology
- RNA Biology
Background:
- Keloids are pathological scars with excessive collagen.
- Current keloid therapies are limited due to poor understanding of molecular drivers.
- N6-methyladenosine (m6A) RNA modification is implicated in fibrosis, but its role in keloids is unknown.
Purpose of the Study:
- Investigate the role and mechanism of METTL3 in keloid fibrosis.
- Determine if METTL3 is a potential therapeutic target for keloid treatment.
Main Methods:
- RNA sequencing of keloid and normal skin tissues.
- Knockdown of METTL3 in primary keloid fibroblasts (KF).
- In vivo studies using a rat scar model with METTL3 shRNA delivery.
Main Results:
- METTL3 was upregulated in keloid tissues and KF, promoting proliferation, migration, and apoptosis resistance.
- METTL3 knockdown suppressed pro-fibrotic phenotypes and reduced key fibrotic markers (α-SMA, TGF-β1, COL1A1).
- METTL3 stabilized COL1A1 mRNA via m6A modification, enhancing translation through YTHDF1, forming an m6A-YTHDF1-COL1A1 axis.
Conclusions:
- METTL3 is a key regulator of keloid fibrosis.
- The m6A-YTHDF1-COL1A1 axis drives excessive collagen deposition in keloids.
- METTL3 inhibition presents a promising therapeutic strategy for pathological scarring.
More Related Videos
Related Concept Videos
01:23Role of Matrix Metalloproteases in Degradation of ECM
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
A...
01:13Cell-matrix's Response to Mechanical Forces
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
01:11Fibril-associated Collagen
Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
01:29The Extracellular Matrix
Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
01:42The Extracellular Matrix
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.Composition of the Extracellular MatrixThe extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse molecules.
01:24Overview of Cell-Matrix Interactions
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...