GO:1904754 positive regulation of vascular associated smooth muscle cell migration: Signaling Pathways, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1904754 describes any process that activates or increases the frequency, rate or extent of vascular associated smooth muscle cell migration.
• Vascular smooth muscle cell (VSMC) migration is a hallmark of neointimal hyperplasia, atherosclerosis, in-stent restenosis and pulmonary vascular remodeling.
• Key positive regulators include LDHA-driven lactate production, c-Fos/IL-17C signaling, PKG1, and matricellular proteins.
• Loss of contractile markers such as KCNMB1 or SNHG18 promotes a phenotypic switch that enhances VSMC migration.
• CRISPR knockout, point-mutation, knock-in and overexpression models are essential to establish causality for candidate regulators of VSMC migration.
• EDITGENE provides end-to-end CRISPR cell model and library screening services to dissect GO:1904754-related mechanisms.
Description
GO:1904754, positive regulation of vascular associated smooth muscle cell migration, is a biological process term that captures any molecular event that activates or increases the frequency, rate or extent of vascular associated smooth muscle cell migration. Vascular smooth muscle cells (VSMCs) are the predominant cellular component of the arterial media, and their migration from the media into the intima is a critical step in vascular remodeling and disease. Understanding the positive regulators of this process is therefore central to vascular biology and to the development of therapies for occlusive vascular diseases.
positive regulation of vascular associated smooth muscle cell migration At A Glance
| GO ID | GO:1904754 |
|---|---|
| GO term | positive regulation of vascular associated smooth muscle cell migration |
| Ontology | biological_process |
| Synonym | activation of vascular smooth muscle cell migration; upregulation of vascular associated smooth muscle cell migration |
| Major function | Increases the frequency, rate or extent of VSMC migration |
| Related process | VSMC phenotypic switch, neointimal hyperplasia, vascular remodeling |
| Cellular context | Arterial media, neointima, atherosclerotic plaque, pulmonary vasculature |
| Disease relevance | Atherosclerosis, in-stent restenosis, pulmonary hypertension, hemorrhoidal disease |
What Is GO:1904754?
In plain terms, GO:1904754 refers to any process that turns up or accelerates the movement of vascular associated smooth muscle cells. It is a child of the broader regulation of vascular associated smooth muscle cell migration and is defined by QuickGO as any process that activates or increases the frequency, rate or extent of vascular associated smooth muscle cell migration. This term is used when a gene product, signaling pathway, or environmental cue promotes VSMC motility, as opposed to inhibiting it.
Why Is positive regulation of vascular associated smooth muscle cell migration Important in Cell Biology?
Positive regulation of VSMC migration is a double-edged sword: it is required for physiological vascular repair, but when dysregulated it drives pathological intimal thickening, restenosis, and pulmonary vascular remodeling. Identifying the molecular drivers of this process provides mechanistic insight into vascular disease and reveals candidate therapeutic targets.
• VSMC migration from the media to the intima is a defining event in neointimal hyperplasia and in-stent restenosis.
• LDHA-mediated lactate generation promotes pulmonary vascular remodeling by enhancing VSMC migration.
• Chlamydia pneumoniae infection promotes VSMC migration via c-Fos/interleukin-17C signaling, linking infection to vascular pathology.
• PKG1 promotes HIV-induced proliferation, migration, and fibrosis of VSMCs in hemorrhoidal disease.
• Matricellular proteins in the extracellular matrix modulate VSMC migration during atherosclerosis development.
• Loss of KCNMB1 induces VSMC phenotypic switch and apoptosis, altering contractile and migratory behavior.
• SNHG18 controls the VSMC contractile phenotype and neointimal hyperplasia, implicating lncRNAs in migration regulation.
• NONRATT000538.2 promotes VSMC phenotypic switch and in-stent restenosis, highlighting non-coding RNA regulators.
• Understanding positive regulators supports development of anti-restenotic and anti-atherosclerotic therapies.
• CRISPR-based models enable causal testing of candidate positive regulators in VSMC migration.
What Happens During positive regulation of vascular associated smooth muscle cell migration?
Initiation by extracellular and metabolic cues
In simple terms: The process starts when signals outside or inside the cell tell the VSMC to start moving.
Positive regulation of VSMC migration is initiated by diverse cues including metabolic shifts, infection, and matricellular matrix remodeling. LDHA-mediated lactate generation promotes pulmonary vascular remodeling and enhances VSMC migratory capacity. Chlamydia pneumoniae infection activates c-Fos/interleukin-17C signaling to promote VSMC migration. Matricellular proteins in the atherosclerotic microenvironment also provide pro-migratory signals.
Phenotypic switch from contractile to synthetic
In simple terms: The cell changes its identity from a quiet contractile cell to a mobile synthetic cell.
A key step in positive regulation of VSMC migration is the phenotypic switch from a contractile to a synthetic, migratory state. Reduced expression of KCNMB1 leads to VSMC phenotypic switch and apoptosis, altering normal contractile behavior. SNHG18 controls the VSMC contractile phenotype, and its dysregulation is linked to neointimal hyperplasia. NONRATT000538.2 promotes VSMC phenotypic switch and in-stent restenosis, demonstrating that non-coding RNAs can drive this transition.
Cytoskeletal reorganization and motility machinery
In simple terms: The cell rearranges its internal skeleton to crawl forward.
Once the phenotypic switch occurs, VSMCs reorganize their cytoskeleton to enable directional migration. PKG1 promotes HIV-induced proliferation, migration, and fibrosis of VSMCs, indicating that kinase signaling directly supports the motility machinery. The c-Fos/IL-17C axis further amplifies pro-migratory signaling in infected VSMCs. These events converge on actin dynamics and focal adhesion turnover that power cell movement.
Extracellular matrix remodeling and invasion
In simple terms: The moving cell clears a path through the surrounding matrix.
Migrating VSMCs degrade and remodel the extracellular matrix to invade the intima. Matricellular proteins in atherosclerosis development modulate this matrix environment and influence VSMC migration. LDHA-mediated lactate production may also alter the metabolic and matrix milieu in pulmonary hypertension. This remodeling step is essential for neointimal hyperplasia and in-stent restenosis.
Amplification and feed-forward loops
In simple terms: The process reinforces itself so migration continues.
Positive regulation of VSMC migration often involves feed-forward loops. c-Fos/interleukin-17C signaling can sustain inflammatory and migratory programs. PKG1 supports proliferation, migration, and fibrosis, creating a self-reinforcing pathological cycle in hemorrhoidal VSMCs. SNHG18 and NONRATT000538.2 represent lncRNA nodes that can amplify phenotypic switching and neointimal hyperplasia.
Key Genes Involved in GO:1904754 positive regulation of vascular associated smooth muscle cell migration
The following genes and proteins have been experimentally linked to positive regulation of vascular associated smooth muscle cell migration or to the VSMC phenotypic switch that enables it.
| Gene | Major Role | Research Relevance |
|---|---|---|
| LDHA | Lactate generation promoting pulmonary vascular remodeling | Metabolic driver of VSMC migration in pulmonary hypertension |
| KCNMB1 | Maintains VSMC contractile phenotype | Loss leads to phenotypic switch and apoptosis |
| SNHG18 | Controls VSMC contractile phenotype | lncRNA regulator of neointimal hyperplasia |
| FOS (c-Fos) | Transcription factor mediating infection-induced migration | c-Fos/IL-17C signaling promotes VSMC migration |
| IL17C | Pro-inflammatory cytokine | Mediates Chlamydia pneumoniae-induced VSMC migration |
| PRKG1 (PKG1) | Kinase promoting proliferation, migration, fibrosis | HIV-induced VSMC pathology in hemorrhoids |
| NONRATT000538.2 | lncRNA promoting phenotypic switch | Drives in-stent restenosis |
| Matricellular proteins (e.g., thrombospondins, tenascins) | Modulate extracellular matrix and migration | Atherosclerosis development |
| ACTA2 | Contractile marker of VSMCs | Readout of phenotypic switch |
| MYH11 | Contractile marker of VSMCs | Readout of phenotypic switch |
| MMP2 | Matrix metalloproteinase for matrix degradation | Facilitates VSMC invasion |
| MMP9 | Matrix metalloproteinase for matrix degradation | Facilitates VSMC invasion |
| TGFB1 | Cytokine modulating VSMC phenotype | Context-dependent regulator of migration |
| PDGF-BB | Growth factor stimulating VSMC migration | Classic pro-migratory stimulus |
| IL-17C receptor complex | Mediates IL-17C signaling | Target for infection-associated migration |
| cGMP-dependent protein kinase | Signaling node in VSMC motility | PKG1-related pathway |
| Lactate transporters (MCTs) | Export/import lactate | Linked to LDHA-driven remodeling |
How Is positive regulation of vascular associated smooth muscle cell migration Regulated?
Positive regulation of VSMC migration is controlled by a layered network of metabolic, inflammatory, and non-coding RNA signals. LDHA-mediated lactate generation acts as a metabolic regulator that promotes pulmonary vascular remodeling. Inflammatory signaling through c-Fos/interleukin-17C regulates migration in the context of Chlamydia pneumoniae infection. PKG1 signaling promotes HIV-induced proliferation, migration, and fibrosis of VSMCs. Non-coding RNAs such as SNHG18 and NONRATT000538.2 regulate the VSMC contractile phenotype and neointimal hyperplasia, thereby indirectly controlling migratory capacity. Matricellular proteins in the extracellular matrix provide additional regulatory input during atherosclerosis.
positive regulation of vascular associated smooth muscle cell migration and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| LDHA | Pulmonary hypertension | LDHA knockout VSMC line; hypoxia-induced pulmonary hypertension model |
| SNHG18 | Neointimal hyperplasia | SNHG18 knockout/overexpression in VSMCs; carotid injury model |
| NONRATT000538.2 | In-stent restenosis | lncRNA knockout/overexpression in VSMCs; stent injury model |
| FOS/IL17C | Infection-associated vascular remodeling | c-Fos or IL-17C knockout VSMCs; Chlamydia pneumoniae infection model |
| PRKG1 | HIV-associated hemorrhoidal disease | PKG1 knockout/overexpression in VSMCs; HIV-related fibrosis model |
Atherosclerosis and neointimal hyperplasia
Positive regulation of VSMC migration is central to atherosclerosis and neointimal hyperplasia. Matricellular proteins in the atherosclerotic microenvironment modulate VSMC behavior and plaque progression. SNHG18 controls the VSMC contractile phenotype and neointimal hyperplasia, linking lncRNA regulation to occlusive vascular disease. NONRATT000538.2 promotes VSMC phenotypic switch and in-stent restenosis, a clinically important complication after stent placement.
Pulmonary hypertension
In pulmonary hypertension, LDHA-mediated lactate generation promotes pulmonary vascular remodeling, in part by enhancing VSMC migratory and proliferative programs. This metabolic axis represents a potential therapeutic target for halting or reversing pulmonary vascular remodeling.
Infection-associated vascular pathology
Chlamydia pneumoniae infection promotes VSMC migration via c-Fos/interleukin-17C signaling, providing a mechanistic link between infection and vascular remodeling. This suggests that anti-inflammatory or anti-IL-17C strategies could modulate VSMC migration in infected vessels.
Hemorrhoidal disease and HIV-associated vascular remodeling
PKG1 promotes HIV-induced proliferation, migration, and fibrosis of VSMCs in hemorrhoids, indicating that positive regulation of VSMC migration contributes to hemorrhoidal pathology in the setting of HIV. This highlights the broad relevance of GO:1904754 beyond classic cardiovascular diseases.
From positive regulation of vascular associated smooth muscle cell migration-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is LDHA required for VSMC migration? | LDHA knockout VSMC line |
| Does SNHG18 loss alter contractile phenotype? | SNHG18 knockout VSMC line |
| Does NONRATT000538.2 drive in-stent restenosis? | lncRNA overexpression and knockout VSMCs |
| Does c-Fos mediate infection-induced migration? | c-Fos point-mutation or knockout VSMCs |
| Does PKG1 promote VSMC fibrosis? | PKG1 knock-in or overexpression VSMCs |
| Do matricellular proteins modulate migration? | Matricellular protein knockout or tagged knock-in VSMCs |
How to Study the positive regulation of vascular associated smooth muscle cell migration Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Transwell migration assay | Number of migrated VSMCs | Quantify positive regulation of VSMC migration |
| Scratch-wound assay | Rate of VSMC monolayer closure | Assess pro-migratory cues |
| RNA-seq | Transcriptome changes during phenotypic switch | Identify lncRNAs and mRNAs |
| Immunoblotting | Protein levels of LDHA, c-Fos, IL-17C, PKG1 | Validate signaling changes |
| Lactate assay | Lactate production | Link LDHA activity to migration |
| Immunofluorescence | ACTA2, MYH11, cytoskeletal organization | Confirm phenotypic switch |
| Carotid injury model | Neointimal hyperplasia | In vivo validation of migration regulators |
| Stent implantation model | In-stent restenosis | Test lncRNA or gene function in vivo |
Transcriptomic and phenotypic profiling
RNA-seq of VSMCs under pro-migratory stimuli can identify genes and lncRNAs such as SNHG18 and NONRATT000538.2 that are differentially expressed during phenotypic switch. Contractile markers like ACTA2 and MYH11 serve as readouts of the switch.
Migration assays
Transwell and scratch-wound assays quantify the frequency and rate of VSMC migration in response to cues such as PDGF-BB, lactate, or infection. These assays are the direct functional readout for GO:1904754.
Metabolic and signaling analysis
Lactate measurement, Seahorse analysis, and immunoblotting for LDHA, c-Fos, IL-17C, and PKG1 can dissect the metabolic and signaling inputs that positively regulate VSMC migration.
In vivo vascular injury models
Carotid artery ligation, stent implantation, and pulmonary hypertension models allow assessment of neointimal hyperplasia and vascular remodeling in vivo. These models validate in vitro findings and establish causality.
How CRISPR Can Be Used to Study GO:1904754 positive regulation of vascular associated smooth muscle cell migration
Knockout
CRISPR knockout of candidate genes such as LDHA, SNHG18, or NONRATT000538.2 in VSMCs can determine whether they are required for positive regulation of migration. Loss-of-function models are the first step in establishing causality.
Point Mutation
Point mutations in signaling nodes like c-Fos or PKG1 can dissect specific phosphorylation or DNA-binding residues that mediate pro-migratory signaling. This approach refines mechanistic understanding beyond simple knockout.
Knock-in
Knock-in of tagged alleles (e.g., GFP or HA tags) at endogenous loci allows tracking of proteins such as PKG1 or LDHA during VSMC migration. Tagged knock-ins also enable chromatin immunoprecipitation and interaction studies.
Overexpression
Overexpression of lncRNAs like NONRATT000538.2 or SNHG18 in VSMCs can test sufficiency for inducing phenotypic switch and migration. Overexpression models complement knockout studies to establish bidirectional causality.
How EDITGENE Supports positive regulation of vascular associated smooth muscle cell migration Research
Researchers studying positive regulation of vascular associated smooth muscle cell migration-related genes often need to determine whether a candidate gene is causally involved in VSMC phenotypic switch and motility. EDITGENE provides the CRISPR cell model and screening services required to move from correlation to causation.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of vascular associated smooth muscle cell migration research.
Frequently Asked Questions About positive regulation of vascular associated smooth muscle cell migration
What is GO:1904754?
GO:1904754 is the Gene Ontology term for positive regulation of vascular associated smooth muscle cell migration, defined as any process that activates or increases the frequency, rate or extent of VSMC migration.
What genes are involved in positive regulation of vascular smooth muscle cell migration?
Key genes include LDHA, KCNMB1, SNHG18, FOS, IL17C, PRKG1, and NONRATT000538.2, as well as matricellular proteins.
How is VSMC migration measured experimentally?
Transwell and scratch-wound assays are standard methods to quantify VSMC migration in vitro.
What diseases involve positive regulation of VSMC migration?
Atherosclerosis, neointimal hyperplasia, in-stent restenosis, pulmonary hypertension, and HIV-associated hemorrhoidal disease.
Does LDHA promote VSMC migration?
Yes, LDHA-mediated lactate generation promotes pulmonary vascular remodeling, which involves enhanced VSMC migration.
What is the role of c-Fos in VSMC migration?
c-Fos mediates Chlamydia pneumoniae-induced VSMC migration via interleukin-17C signaling.
How does PKG1 affect VSMCs?
PKG1 promotes HIV-induced proliferation, migration, and fibrosis of VSMCs in hemorrhoids.
What is the VSMC phenotypic switch?
It is the transition from a contractile to a synthetic, migratory state, regulated by genes such as KCNMB1 and SNHG18.
Can CRISPR be used to study VSMC migration?
Yes, CRISPR knockout, point-mutation, knock-in, and overexpression models are used to test causality for candidate regulators.
What services does EDITGENE provide for VSMC migration research?
EDITGENE provides CRISPR knockout, point-mutation, knock-in, overexpression cell models, CRISPR library screening, and bioinformatics services.
Conclusion
GO:1904754, positive regulation of vascular associated smooth muscle cell migration, is a central biological process in vascular remodeling and disease. Experimental evidence implicates metabolic, inflammatory, kinase, and non-coding RNA pathways in driving VSMC migration. CRISPR-based models are essential to establish causality and to identify new therapeutic targets. EDITGENE offers comprehensive services to accelerate this research.
References
- 2. Wu D et al.. 2024. Lactate dehydrogenase A (LDHA)-mediated lactate generation promotes pulmonary vascular remodeling in pulmonary hypertension.. J Transl Med 22(1):738 PMID: 39103838
- 3. Liu H et al.. 2025. Reduced expression of KCNMB1 leads to vascular smooth muscle cell phenotypic switch and apoptosis.. Biochem Pharmacol 241:117151 PMID: 40653026
- 4. Niu K et al.. 2024. Small nucleolar RNA host gene 18 controls vascular smooth muscle cell contractile phenotype and neointimal hyperplasia.. Cardiovasc Res 120(7):796-810 PMID: 38498586
- 5. Pervaiz N et al.. 2023. Matricellular proteins in atherosclerosis development.. Matrix Biol 120:1-23 PMID: 37086928
- 6. Zhao J et al.. 2024. NONRATT000538.2 promotes vascular smooth muscle cell phenotypic switch and in-stent restenosis.. Exp Cell Res 442(2):114260 PMID: 39303839
- 7. Zheng N et al.. 2019. Chlamydia pneumoniae infection promotes vascular smooth muscle cell migration via c-Fos/interleukin-17C signaling.. Int J Med Microbiol 309(8):151340 PMID: 31494039
- 8. Li Z et al.. 2024. PKG1 promotes the HIV-induced proliferation, migration, and fibrosis of vascular smooth muscle cells of hemorrhoids.. Int J Colorectal Dis 39(1):175 PMID: 39477875
