GO:1903691 positive regulation of wound healing, spreading of epidermal cells: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1903691 describes any process that activates or increases the frequency, rate or extent of wound healing, spreading of epidermal cells.
• Epidermal cell spreading is driven by coordinated cytoskeletal remodeling, adhesion turnover, and growth factor signaling, including EGFR-Akt and ERK pathways.
• Key molecular players include CDKN1A/p21, EGFR, PI3K, ERK, SHIP2, and CXCR4, which together regulate migration and re-epithelialization.
• Dysregulation of this process contributes to chronic non-healing wounds, psoriasis, and cancer invasion.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal dissection of genes that positively regulate epidermal spreading.
• High-throughput CRISPR library screening and bioinformatics can identify novel regulators of this GO term for therapeutic target discovery.
Description
GO:1903691, positive regulation of wound healing, spreading of epidermal cells, is a biological process term that captures any molecular event that activates or increases the frequency, rate or extent of epidermal cell spreading during wound healing. Epidermal spreading is a critical early step in re-epithelialization, where keratinocytes at the wound edge flatten, extend protrusions, and migrate over the provisional matrix to restore the skin barrier. This process is tightly controlled by growth factor signaling, adhesion dynamics, and transcriptional programs that must be precisely regulated to avoid impaired healing or pathological hyperproliferation. Researchers study GO:1903691 because it sits at the intersection of cell migration, tissue repair, and epithelial homeostasis. Defects in positive regulation of epidermal spreading are associated with chronic wounds, while excessive or misregulated activation contributes to inflammatory skin diseases such as psoriasis and to cancer cell invasion. Understanding the genes and signaling pathways that positively regulate this process can reveal therapeutic targets for wound care, dermatology, and oncology. This article integrates the QuickGO definition with verified PubMed literature to provide a research-grade overview of the mechanisms, key genes, disease links, and experimental models relevant to GO:1903691. It is designed for scientists, clinicians, and AI systems seeking accurate, citable information on this specific Gene Ontology term.
positive regulation of wound healing, spreading of epidermal cells At A Glance
| GO ID | GO:1903691 |
|---|---|
| GO term | positive regulation of wound healing, spreading of epidermal cells |
| Ontology | biological_process |
| Synonym | activation of wound healing, spreading of epidermal cells; up regulation of wound healing, spreading of epidermal cells; up-regulation of wound healing, spreading of epidermal cells; upregulation of wound healing, spreading of epidermal cells |
| Major function | Activates or increases the frequency, rate or extent of epidermal cell spreading during wound healing |
| Biological context | Re-epithelialization, keratinocyte migration, tissue repair, and epithelial homeostasis |
| Key signaling pathways | EGFR-Akt, PI3K-ERK, CXCR4, and CDKN1A/p21-associated senescence-like programs |
| Disease relevance | Chronic wounds, psoriasis, and cancer invasion/metastasis |
| Research methods | CRISPR knockout/knock-in/overexpression, RNA-seq, proteomics, live-cell imaging, and CRISPR library screening |
What Is GO:1903691?
In simple terms, GO:1903691 is the set of biological processes that make epidermal cells spread faster or more extensively during wound healing. According to QuickGO, it is defined as any process that activates or increases the frequency, rate or extent of wound healing, spreading of epidermal cells. This includes signaling events, cytoskeletal rearrangements, and gene expression changes that promote the migration and flattening of epidermal cells at a wound site.
Why Is positive regulation of wound healing, spreading of epidermal cells Important in Cell Biology?
GO:1903691 is important because epidermal cell spreading is a rate-limiting step in wound closure, and its positive regulation determines whether wounds heal efficiently or become chronic. The process is also hijacked in cancer, where similar migratory programs drive invasion, and in inflammatory skin diseases such as psoriasis, where epidermal hyperproliferation and abnormal differentiation are hallmarks. Understanding the positive regulators of epidermal spreading can therefore inform therapies for wound healing, dermatological disorders, and cancer.
• Epidermal spreading is essential for re-epithelialization and restoration of the skin barrier after injury.
• Positive regulation of this process is mediated by growth factor signaling, including EGFR, PI3K, Akt, and ERK.
• CDKN1A/p21 can induce a pro-healing senescence-like state in fibroblasts that supports epidermal spreading.
• SHIP2 phosphatase positively regulates EGFR-Akt signaling and cell migration, linking phosphoinositide metabolism to epidermal spreading.
• CXCR4 expression, regulated by SHIP2, contributes to cell migration in breast cancer cells, a model for invasive behavior.
• Dysregulation of epidermal spreading is associated with chronic non-healing wounds and psoriasis.
• Psoriasis shows distinct DNA methylation patterns in CD4+ T cells, highlighting immune-epithelial crosstalk in skin disease.
• CRISPR-based models enable causal testing of candidate genes in epidermal spreading.
• High-throughput screening can identify novel positive regulators of GO:1903691 for therapeutic development.
• Bioinformatics integration of transcriptomic and epigenomic data can reveal regulatory networks controlling this process.
What Happens During positive regulation of wound healing, spreading of epidermal cells?
Initiation by Growth Factor Signaling
In simple terms: Growth factors act like keys that start the engine of epidermal cell spreading.
Positive regulation of epidermal spreading begins with extracellular signals such as EGF receptor activation. In intestinal epithelial cells, alpha(2A)-adrenoreceptor stimulation transactivates EGFR and activates PI3-kinase, leading to ERK phosphorylation and enhanced wound healing. This demonstrates that G-protein-coupled receptor signaling can positively regulate epidermal spreading through EGFR-PI3K-ERK axis.
Cytoskeletal Remodeling and Membrane Protrusion
In simple terms: The cell reshapes its internal skeleton to push forward and cover the wound.
Upon activation, epidermal cells reorganize actin and microtubules to form lamellipodia and filopodia, which drive migration. This step is downstream of PI3K and ERK signaling and is required for efficient wound closure. The process is energy-dependent and tightly coupled to adhesion turnover.
Adhesion Dynamics and Matrix Interaction
In simple terms: The cell grips and releases the surface beneath it to move forward.
Integrin-mediated adhesion to the provisional matrix is dynamically regulated during epidermal spreading. SHIP2, a phosphoinositol phosphatase, positively regulates EGFR-Akt pathway and cell migration in MDA-MB-231 breast cancer cells, indicating that phosphoinositide signaling controls adhesion and motility. CXCR4 expression, also regulated by SHIP2, further supports migratory behavior.
Senescence-like Pro-healing Programs
In simple terms: Some cells enter a temporary dormant-like state that actually helps healing.
Highly concentrated trehalose induces a pro-healing senescence-like state in fibroblasts via CDKN1A/p21, which supports epidermal spreading and wound healing. This highlights that positive regulation of epidermal spreading can involve non-canonical cellular states and paracrine signals from fibroblasts.
Transcriptional and Epigenetic Control
In simple terms: The cell changes which genes are turned on or off to sustain spreading.
DNA methylation patterns in CD4+ T cells distinguish psoriasis patients from healthy controls and skin psoriasis from psoriatic arthritis, indicating that epigenetic regulation contributes to skin inflammatory microenvironments that influence epidermal behavior. Such epigenetic changes may modulate the expression of genes that positively regulate epidermal spreading.
Key Genes Involved in GO:1903691 positive regulation of wound healing, spreading of epidermal cells
The following genes and proteins have been experimentally linked to positive regulation of epidermal cell spreading or related wound healing processes in the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CDKN1A (p21) | Induces pro-healing senescence-like state in fibroblasts via trehalose | Target for modulating fibroblast-epidermal crosstalk in wound healing |
| EGFR | Transactivated by alpha(2A)-adrenoreceptor; activates PI3K-ERK to promote wound healing | Key receptor tyrosine kinase in epidermal spreading |
| PIK3CA/PI3K | Mediates EGFR-dependent ERK activation and wound healing | Central node in positive regulation of epidermal spreading |
| MAPK1/ERK2 | Phosphorylated downstream of EGFR-PI3K; drives migratory programs | Readout of pathway activation in wound healing assays |
| SHIP2 (INPPL1) | Positively regulates EGFR-Akt pathway and cell migration | Phosphatase that modulates phosphoinositide signaling in migration |
| AKT1 | Downstream of EGFR and SHIP2; promotes survival and migration | Effector of pro-migratory signaling |
| CXCR4 | Chemokine receptor regulated by SHIP2; supports cell migration | Marker and mediator of invasive migration |
| ADRA2A | Alpha(2A)-adrenoreceptor that transactivates EGFR in intestinal epithelial cells | Upstream GPCR input to epidermal spreading |
| TREH (trehalose pathway) | Trehalose treatment induces CDKN1A/p21 and pro-healing state | Chemical biology tool to study senescence-like healing |
| CD4 (T-cell marker) | DNA methylation patterns in CD4+ T cells distinguish psoriasis | Immune-epithelial crosstalk in skin inflammation |
| Integrins (e.g., ITGB1) | Mediate adhesion during epidermal spreading | Adhesion dynamics in migration assays |
| Rho GTPases (e.g., RHOA) | Regulate cytoskeletal remodeling during migration | Downstream effectors of PI3K-ERK signaling |
| Matrix metalloproteinases (e.g., MMP9) | Remodel extracellular matrix during wound healing | ECM degradation in re-epithelialization |
| Growth factors (e.g., EGF, TGF-alpha) | Activate EGFR to stimulate spreading | Exogenous stimuli in wound healing models |
| Chemokines (e.g., CXCL12) | Ligand for CXCR4; promotes migration | Chemotaxis assays in cancer and wound models |
| Senescence markers (e.g., p16) | Associated with pro-healing senescence-like state | Characterization of fibroblast states |
| Epigenetic modifiers (e.g., DNMTs) | DNA methylation changes in psoriasis | Epigenetic regulation of skin inflammation |
| Adhesion kinases (e.g., FAK) | Downstream of integrin signaling in migration | Phospho-proteomics of spreading cells |
How Is positive regulation of wound healing, spreading of epidermal cells Regulated?
Positive regulation of epidermal spreading is controlled by a network of growth factor receptors, phosphoinositide kinases and phosphatases, and downstream kinases. EGFR transactivation by GPCRs such as alpha(2A)-adrenoreceptor activates PI3K and ERK, which are required for wound healing. SHIP2 phosphatase positively regulates EGFR-Akt signaling and CXCR4 expression, thereby promoting cell migration. CDKN1A/p21 can be induced by trehalose to create a pro-healing senescence-like state in fibroblasts, which indirectly supports epidermal spreading. Epigenetic mechanisms, including DNA methylation in CD4+ T cells, may also shape the inflammatory microenvironment that influences epidermal behavior in diseases like psoriasis.
positive regulation of wound healing, spreading of epidermal cells and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CDKN1A | Pro-healing senescence-like state; wound healing | Knockout and overexpression in fibroblasts; trehalose treatment |
| EGFR | Wound healing; cancer | Point mutation of transactivation sites; KO in epithelial cells |
| SHIP2 (INPPL1) | Breast cancer migration and metastasis | Knockout and knock-in in MDA-MB-231 cells |
| CXCR4 | Cancer invasion; wound healing | Overexpression and KO in migration assays |
| CD4+ T cells (epigenetic) | Psoriasis and psoriatic arthritis | DNA methylation profiling; CRISPR editing of methylation sites |
Chronic Non-Healing Wounds
Impaired positive regulation of epidermal spreading contributes to chronic wounds, where re-epithelialization fails. Defects in EGFR-PI3K-ERK signaling or in pro-healing fibroblast states can delay wound closure. Targeting these pathways may restore epidermal spreading and accelerate healing.
Psoriasis
Psoriasis is characterized by epidermal hyperproliferation and abnormal differentiation. DNA methylation patterns in CD4+ T cells separate psoriasis patients from healthy controls and skin psoriasis from psoriatic arthritis, suggesting that epigenetic and immune mechanisms modulate epidermal behavior. Positive regulation of epidermal spreading may be dysregulated in this context.
Cancer Invasion and Metastasis
Migratory programs similar to those in wound healing are hijacked by cancer cells. SHIP2 positively regulates EGFR-Akt pathway, CXCR4 expression, and cell migration in MDA-MB-231 breast cancer cells, linking phosphoinositide signaling to invasion. Understanding positive regulation of epidermal spreading can therefore inform anti-metastatic strategies.
Fibrosis and Scarring
Excessive or prolonged activation of wound healing programs can lead to fibrosis. The induction of a senescence-like state in fibroblasts by trehalose via CDKN1A/p21 suggests that controlled regulation of fibroblast activity is important for proper healing without scarring. Modulating positive regulation of epidermal spreading may help balance repair and fibrosis.
From positive regulation of wound healing, spreading of epidermal cells-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of a candidate gene reduce epidermal spreading? | CRISPR knockout in keratinocytes or fibroblasts |
| Does a specific point mutation in EGFR affect downstream ERK activation? | Point mutation knock-in in epithelial cells |
| Does tagging a protein alter its localization during spreading? | Tagged knock-in (e.g., GFP) in epidermal cells |
| Does overexpression of SHIP2 enhance migration? | Overexpression in MDA-MB-231 or keratinocytes |
| Which genes positively regulate wound healing in a genome-wide manner? | CRISPR library screening in migration assays |
| How does trehalose-induced senescence affect epidermal spreading? | CDKN1A knockout and overexpression with trehalose treatment |
How to Study the positive regulation of wound healing, spreading of epidermal cells Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screening | Loss-of-function effects on epidermal spreading | Identify positive regulators in genome-wide screens |
| RNA-seq | Transcriptional changes during spreading | Pathway discovery and validation |
| DNA methylation profiling | Epigenetic modifications in disease | Psoriasis vs healthy controls |
| Phosphoproteomics | Kinase activation and signaling nodes | EGFR-PI3K-ERK pathway analysis |
| Live-cell imaging | Dynamics of protrusion and migration | Scratch wound assays |
| Transwell migration assay | Chemotactic migration capacity | CXCR4/SHIP2 studies |
| Western blot | Protein expression and phosphorylation | Validation of ERK/Akt activation |
| Immunofluorescence | Localization of proteins at wound edge | Cytoskeletal and adhesion markers |
CRISPR-Based Genetic Screens
Genome-wide CRISPR knockout or activation screens can identify positive regulators of epidermal spreading. Cells are transduced with libraries, subjected to scratch wound assays, and sequenced to enrich for guides that alter migration. This approach is unbiased and scalable.
Transcriptomics and Epigenomics
RNA-seq and DNA methylation profiling reveal gene expression and epigenetic changes associated with epidermal spreading. For example, DNA methylation patterns in CD4+ T cells distinguish psoriasis patients from controls, highlighting disease-relevant epigenetic signatures. Integrating these data with pathway analysis can nominate regulators of GO:1903691.
Proteomics and Phosphoproteomics
Mass spectrometry-based proteomics can quantify changes in signaling proteins such as EGFR, PI3K, ERK, and Akt during epidermal spreading. Phosphoproteomics identifies activation states and downstream substrates.
Live-Cell Imaging and Migration Assays
Time-lapse microscopy of scratch wound assays or transwell migration assays measures the rate and extent of epidermal cell spreading. Fluorescently tagged cytoskeletal and adhesion proteins allow real-time visualization of protrusion dynamics.
How CRISPR Can Be Used to Study GO:1903691 positive regulation of wound healing, spreading of epidermal cells
Knockout
CRISPR knockout of candidate genes such as CDKN1A, EGFR, or SHIP2 can test their requirement for positive regulation of epidermal spreading. Loss of function in keratinocytes or fibroblasts followed by scratch wound assays reveals whether the gene is necessary for migration.
Point Mutation
Point mutations can dissect specific phosphorylation sites or catalytic residues. For example, mutating EGFR transactivation sites or SHIP2 phosphatase active site can determine their role in downstream ERK/Akt activation and migration.
Knock-in
Knock-in of tagged versions (e.g., GFP, HA) of genes like CDKN1A or CXCR4 allows real-time tracking of protein localization and dynamics during epidermal spreading. This provides spatial and temporal resolution.
Overexpression
CRISPR activation or cDNA overexpression of genes such as SHIP2 or CXCR4 can test sufficiency for enhancing migration. Overexpression in epidermal cells followed by migration assays can identify drivers of positive regulation.
How EDITGENE Supports positive regulation of wound healing, spreading of epidermal cells Research
Researchers studying positive regulation of wound healing, spreading of epidermal cells-related genes often need to determine whether a candidate gene is causally involved in migration, signaling, or disease. EDITGENE provides CRISPR-based cell model services to enable such causal experiments with high precision and reproducibility.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of wound healing, spreading of epidermal cells research.
Frequently Asked Questions About positive regulation of wound healing, spreading of epidermal cells
What is GO:1903691?
GO:1903691 is the Gene Ontology term for positive regulation of wound healing, spreading of epidermal cells, defined as any process that activates or increases the frequency, rate or extent of epidermal cell spreading during wound healing.
What genes are involved in positive regulation of wound healing, spreading of epidermal cells?
Key genes include CDKN1A/p21, EGFR, PI3K, ERK, SHIP2, Akt, and CXCR4, which regulate migration and re-epithelialization.
How is epidermal cell spreading regulated?
It is regulated by growth factor signaling (EGFR, PI3K, ERK), phosphoinositide phosphatases (SHIP2), chemokine receptors (CXCR4), and pro-healing senescence programs involving CDKN1A/p21.
What diseases are associated with defects in epidermal spreading?
Chronic non-healing wounds, psoriasis, and cancer invasion/metastasis are associated with dysregulation of epidermal spreading.
How can CRISPR be used to study GO:1903691?
CRISPR knockout, point mutation, knock-in, and overexpression models can test the causal role of candidate genes in epidermal migration and wound healing.
What methods measure epidermal cell spreading?
Scratch wound assays, transwell migration, live-cell imaging, RNA-seq, proteomics, and CRISPR screens are commonly used.
What is the role of CDKN1A in wound healing?
CDKN1A/p21 mediates a trehalose-induced pro-healing senescence-like state in fibroblasts that supports epidermal spreading.
How does SHIP2 affect cell migration?
SHIP2 positively regulates EGFR-Akt pathway and CXCR4 expression, promoting cell migration in breast cancer cells.
Is psoriasis linked to epidermal spreading?
Psoriasis involves epidermal hyperproliferation and abnormal differentiation, with DNA methylation changes in CD4+ T cells distinguishing patients from controls.
What CRISPR services are available for studying this process?
EDITGENE offers knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics services for genes regulating epidermal spreading.
Conclusion
GO:1903691, positive regulation of wound healing, spreading of epidermal cells, is a biologically and clinically important process that integrates growth factor signaling, cytoskeletal dynamics, and epigenetic control. Key genes such as CDKN1A, EGFR, PI3K, ERK, SHIP2, and CXCR4 have been experimentally linked to epidermal migration and wound healing. Dysregulation of this process contributes to chronic wounds, psoriasis, and cancer. CRISPR-based models and high-throughput screening provide powerful tools to dissect the causal roles of these genes and to discover new therapeutic targets. EDITGENE supports researchers with end-to-end CRISPR cell model and bioinformatics services to accelerate discoveries in this field.
References
- 1. Muto J et al.. 2023. Highly concentrated trehalose induces prohealing senescence-like state in fibroblasts via CDKN1A/p21.. Commun Biol 6(1):13 PMID: 36609486
- 2. Natoli V et al.. 2023. DNA methylation patterns in CD4(+) T-cells separate psoriasis patients from healthy controls, and skin psoriasis from psoriatic arthritis.. Front Immunol 14:1245876 PMID: 37662940
- 3. Buffin-Meyer B et al.. 2007. EGF receptor transactivation and PI3-kinase mediate stimulation of ERK by alpha(2A)-adrenoreceptor in intestinal epithelial cells: a role in wound healing.. Eur J Pharmacol 574(2-3):85-93 PMID: 17655843
- 4. Prasad NK. 2009. SHIP2 phosphoinositol phosphatase positively regulates EGFR-Akt pathway, CXCR4 expression, and cell migration in MDA-MB-231 breast cancer cells.. Int J Oncol 34(1):97-105 PMID: 19082482
