GO:1904738 vascular associated smooth muscle cell migration: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1904738 (vascular associated smooth muscle cell migration) is the biological process describing the orderly movement of a vascular smooth muscle cell from one site to another.
• Vascular smooth muscle cell (VSMC) migration is a hallmark of vascular remodeling and contributes to neointimal hyperplasia, atherosclerosis, and hypertension.
• Migration is driven by cytoskeletal reorganization, extracellular matrix remodeling, and growth factor signaling, including PDGFR and JAK2/STAT pathways.
• Key regulators include ANGPTL8, RBM24, LONP1, heme oxygenase-1, and circular RNAs such as hsa_circ_0001402.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal testing of candidate genes in VSMC migration.
• EDITGENE provides end-to-end CRISPR cell model and library screening services to accelerate vascular biology research.
Description
Vascular associated smooth muscle cell migration (GO:1904738) is defined as the orderly movement of a vascular smooth muscle cell from one site to another. This process is fundamental to vascular development, homeostasis, and repair, but its dysregulation is a central driver of vascular pathology. In the adult vessel wall, vascular smooth muscle cells (VSMCs) are normally quiescent and contractile; upon injury or pathological stimuli, they dedifferentiate, proliferate, and migrate, contributing to neointimal hyperplasia and atherosclerosis. Understanding the molecular control of VSMC migration is therefore critical for developing therapies that limit pathological vascular remodeling without compromising essential repair functions. The migration of VSMCs is orchestrated by a complex interplay of growth factors, extracellular matrix (ECM) components, and intracellular signaling cascades. Platelet-derived growth factor (PDGF) is a potent chemoattractant that activates PDGFR and downstream pathways, while angiotensin II promotes VSMC migration and hypertension through mechanisms involving angiopoietin-like protein 8 (ANGPTL8). Recent studies have identified RNA-binding proteins such as RBM24, which stabilizes JAK2 mRNA and regulates VSMC phenotypic switching and migration. Metabolic regulators like LONP1 facilitate pulmonary artery smooth muscle cell glycolytic reprogramming and migration in pulmonary hypertension. Additionally, circular RNAs and microRNAs, such as hsa_circ_0001402 and miR-183-5p, modulate VSMC proliferation, migration, and autophagy. These findings highlight the diversity of molecular players and the need for robust experimental models to dissect their causal roles. This article provides a research-grade overview of GO:1904738, integrating the QuickGO definition with verified PubMed literature. We cover the biological stages of VSMC migration, key genes and proteins, regulatory mechanisms, disease associations, and state-of-the-art research methods, including CRISPR-based genome editing. The content is designed for researchers, drug developers, and AI-driven knowledge retrieval systems seeking authoritative, citable information on vascular smooth muscle cell migration.
vascular associated smooth muscle cell migration At A Glance
| GO ID | GO:1904738 |
|---|---|
| GO term | vascular associated smooth muscle cell migration |
| Ontology | biological_process |
| Synonym | vascular smooth muscle cell migration |
| Definition | The orderly movement of a vascular associated smooth muscle cell from one site to another. |
| Major function | Directed translocation of vascular smooth muscle cells during development, repair, and pathological remodeling. |
| Related processes | Cell proliferation, phenotypic switching, extracellular matrix remodeling, chemotaxis. |
| Key regulators | PDGFR, JAK2, ANGPTL8, RBM24, LONP1, heme oxygenase-1, circular RNAs. |
| Disease relevance | Atherosclerosis, restenosis, hypertension, pulmonary hypertension, arteriosclerosis. |
What Is GO:1904738?
GO:1904738, vascular associated smooth muscle cell migration, is a biological process defined by the Gene Ontology as the orderly movement of a vascular associated smooth muscle cell from one site to another. This term encompasses the directed translocation of smooth muscle cells that are associated with blood vessels, including those in arteries, veins, and pulmonary vasculature. The synonym vascular smooth muscle cell migration is commonly used in the literature. The process is distinct from proliferation, although the two often occur together during vascular remodeling.
Why Is vascular associated smooth muscle cell migration Important in Cell Biology?
Vascular smooth muscle cell migration is a double-edged sword: it is essential for vascular development and repair, but its excessive activation underlies major cardiovascular diseases. In atherosclerosis and restenosis after angioplasty, VSMCs migrate from the media to the intima, where they contribute to neointimal hyperplasia and plaque instability. In hypertension, angiotensin II promotes VSMC migration and vascular hypertrophy, and deletion of ANGPTL8 in VSMCs prevents these effects. In pulmonary hypertension, metabolic reprogramming of pulmonary artery smooth muscle cells enhances their migratory capacity. Therefore, understanding and targeting VSMC migration is a promising therapeutic strategy for cardiovascular and pulmonary vascular diseases.
• VSMC migration is a hallmark of neointimal hyperplasia and restenosis after vascular injury.
• It contributes to atherosclerotic plaque progression and instability.
• Angiotensin II-induced VSMC migration is linked to hypertension and cardiovascular hypertrophy.
• Pulmonary artery smooth muscle cell migration drives pulmonary vascular remodeling in pulmonary hypertension.
• PDGF signaling is a major driver of VSMC dedifferentiation and migration.
• Circular RNAs and microRNAs regulate VSMC migration and autophagy, offering new therapeutic targets.
• Metabolic enzymes such as LONP1 couple glycolytic reprogramming to VSMC migration.
• Heme oxygenase-1 induction inhibits VSMC proliferation and migration, suggesting antioxidant strategies.
• VSMC migration is a key readout in drug discovery for cardiovascular diseases.
• CRISPR-based models enable causal validation of candidate genes in VSMC migration.
What Happens During vascular associated smooth muscle cell migration?
Initiation and Phenotypic Switching
In simple terms: First, the smooth muscle cell changes from a quiet, contractile state to a migratory, synthetic state.
In response to vascular injury or pathological stimuli such as angiotensin II or PDGF, vascular smooth muscle cells (VSMCs) undergo phenotypic switching from a contractile to a synthetic, dedifferentiated state. This switch involves downregulation of contractile markers and upregulation of migratory and proliferative genes. RBM24 has been shown to regulate this phenotypic switching by stabilizing JAK2 mRNA, thereby promoting VSMC migration and vascular remodeling. Kanglexin, a natural compound, counters VSMC dedifferentiation and arteriosclerosis by inhibiting PDGFR signaling.
Chemotaxis and Directional Sensing
In simple terms: The cell senses chemical signals and starts moving toward them.
VSMCs migrate directionally in response to chemoattractants such as PDGF-BB and angiotensin II. PDGFR activation triggers intracellular signaling cascades that lead to actin cytoskeleton reorganization and formation of lamellipodia and filopodia. Angiopoietin-like protein 8 (ANGPTL8) is emerging as a regulator of VSMC migration; VSMC-specific deletion of ANGPTL8 prevents angiotensin II-promoted hypertension and cardiovascular hypertrophy. The precise sensing of chemotactic gradients involves receptor tyrosine kinases and G-protein coupled receptors, which converge on Rho GTPases to establish cell polarity.
Cytoskeletal Reorganization and Force Generation
In simple terms: The cell's internal skeleton rearranges to push the cell forward.
Migration requires dynamic reorganization of actin filaments and microtubules. Actin polymerization at the leading edge drives membrane protrusion, while actomyosin contraction at the rear retracts the cell body. Key regulators include RhoA, Rac1, and Cdc42, which are activated downstream of growth factor receptors. Heme oxygenase-1 (HO-1) has been shown to inhibit VSMC proliferation and migration, partly through modulation of cytoskeletal dynamics and oxidative stress. The interplay between cytoskeletal remodeling and focal adhesion turnover is essential for efficient migration.
Extracellular Matrix Remodeling and Invasion
In simple terms: The cell breaks down and moves through the surrounding matrix.
VSMCs secrete matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM), facilitating cell invasion. This ECM remodeling is critical for VSMC migration from the media to the intima during neointimal hyperplasia. Circular RNA hsa_circ_0001402 alleviates vascular neointimal hyperplasia by regulating VSMC proliferation, migration, and autophagy through a miR-183-5p-dependent mechanism, highlighting the role of non-coding RNAs in ECM interactions. LONP1 facilitates pulmonary artery smooth muscle cell glycolytic reprogramming by degrading MPC1, which supports the energy demands of migration and matrix invasion in pulmonary hypertension.
Metabolic Reprogramming and Energy Supply
In simple terms: The cell changes how it makes energy to support movement.
Migrating VSMCs require increased ATP production. In pulmonary hypertension, pulmonary artery smooth muscle cells undergo glycolytic reprogramming mediated by LONP1, which degrades MPC1 and shifts metabolism toward glycolysis. This metabolic switch supports the biosynthetic and bioenergetic demands of migration and proliferation. Similarly, in systemic vascular remodeling, VSMCs may adopt a glycolytic phenotype to sustain migration. Targeting metabolic enzymes such as LONP1 could therefore limit pathological VSMC migration.
Key Genes Involved in GO:1904738 vascular associated smooth muscle cell migration
The following genes and proteins have been experimentally implicated in vascular associated smooth muscle cell migration (GO:1904738) based on verified PubMed literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PDGFR | Receptor tyrosine kinase activated by PDGF; drives VSMC dedifferentiation and migration | Target for inhibitors like Kanglexin; key driver of arteriosclerosis |
| ANGPTL8 | Regulates VSMC migration and angiotensin II-induced hypertension | VSMC-specific knockout prevents hypertension and cardiovascular hypertrophy |
| RBM24 | RNA-binding protein stabilizing JAK2 mRNA; regulates VSMC phenotypic switching | Knockdown or knockout reduces VSMC migration and vascular remodeling |
| JAK2 | Non-receptor tyrosine kinase downstream of cytokine receptors; promotes VSMC migration | Target of RBM24-mediated mRNA stabilization |
| LONP1 | Mitochondrial protease degrading MPC1; facilitates glycolytic reprogramming | Knockdown reduces pulmonary artery smooth muscle cell migration |
| MPC1 | Mitochondrial pyruvate carrier; substrate of LONP1 | Degradation by LONP1 promotes glycolysis and migration |
| HMOX1 (HO-1) | Heme oxygenase-1; antioxidant enzyme inhibiting VSMC proliferation and migration | Induction by canagliflozin inhibits VSMC migration |
| hsa_circ_0001402 | Circular RNA regulating VSMC proliferation, migration, and autophagy | Overexpression alleviates neointimal hyperplasia via miR-183-5p |
| miR-183-5p | MicroRNA targeted by hsa_circ_0001402; modulates VSMC phenotype | Inhibition or mimicry affects VSMC migration and autophagy |
| RhoA | Small GTPase regulating actin cytoskeleton and contractility | Key mediator of VSMC migration downstream of growth factors |
| Rac1 | Small GTPase promoting lamellipodia formation and migration | Potential target to modulate VSMC motility |
| Cdc42 | Small GTPase regulating filopodia and cell polarity | Involved in directional VSMC migration |
| MMP2 | Matrix metalloproteinase degrading ECM; facilitates VSMC invasion | Inhibition reduces neointimal hyperplasia |
| MMP9 | Matrix metalloproteinase involved in ECM remodeling during VSMC migration | Biomarker and therapeutic target in vascular remodeling |
| PDGF-BB | Ligand for PDGFR; potent chemoattractant for VSMCs | Used experimentally to induce VSMC migration in vitro |
| Angiotensin II | Vasoactive peptide promoting VSMC migration and hypertension | Used to induce VSMC migration and hypertension models |
| TGF-beta | Cytokine modulating VSMC phenotype and migration | Context-dependent effects on VSMC migration |
| KLF4 | Transcription factor promoting VSMC phenotypic switching | Regulates contractile gene repression during migration |
How Is vascular associated smooth muscle cell migration Regulated?
Vascular smooth muscle cell migration is regulated at multiple levels, including transcriptional, post-transcriptional, and metabolic control. The JAK2/STAT3 pathway is stabilized by RBM24, which binds to JAK2 mRNA and promotes its stability, thereby enhancing VSMC migration and phenotypic switching. PDGFR signaling activates downstream effectors such as PI3K/AKT and MAPK, which regulate cytoskeletal dynamics and gene expression. Metabolic regulation via LONP1-mediated degradation of MPC1 shifts metabolism toward glycolysis, supporting the energy demands of migration in pulmonary hypertension. Additionally, circular RNAs and microRNAs, such as hsa_circ_0001402 and miR-183-5p, fine-tune VSMC migration and autophagy. Heme oxygenase-1 acts as a negative regulator, and its induction by canagliflozin inhibits VSMC proliferation and migration. These layers of regulation provide multiple entry points for therapeutic intervention.
vascular associated smooth muscle cell migration and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ANGPTL8 | Hypertension and cardiovascular hypertrophy | VSMC-specific knockout mouse; angiotensin II infusion |
| RBM24 | Vascular remodeling and neointimal hyperplasia | VSMC-specific knockout or knockdown; carotid artery injury model |
| LONP1 | Pulmonary hypertension | Pulmonary artery smooth muscle cell knockout; hypoxia-induced PH model |
| HMOX1 | Atherosclerosis and restenosis | VSMC overexpression or knockout; canagliflozin treatment |
| PDGFR | Arteriosclerosis and restenosis | VSMC-specific knockout; PDGF-BB stimulation; Kanglexin treatment |
Atherosclerosis and Restenosis
VSMC migration from the media to the intima is a critical step in atherogenesis and restenosis after angioplasty. Migrated VSMCs contribute to neointimal hyperplasia and plaque formation. Circular RNA hsa_circ_0001402 alleviates vascular neointimal hyperplasia by regulating VSMC proliferation, migration, and autophagy, suggesting that non-coding RNAs can be targeted to limit pathological remodeling. PDGFR signaling drives VSMC dedifferentiation and migration, and its inhibition by Kanglexin counters arteriosclerosis.
Hypertension and Cardiovascular Hypertrophy
Angiotensin II promotes VSMC migration and hypertension. VSMC-specific deletion of ANGPTL8 prevents angiotensin II-promoted hypertension and cardiovascular hypertrophy, demonstrating a causal role for VSMC migration in these conditions. Targeting ANGPTL8 or its downstream effectors may offer a novel therapeutic strategy for hypertension.
Pulmonary Hypertension
In pulmonary hypertension, pulmonary artery smooth muscle cells undergo glycolytic reprogramming and increased migration. LONP1 facilitates this process by degrading MPC1, and knockdown of LONP1 reduces migration. This highlights metabolic enzymes as potential therapeutic targets in pulmonary vascular disease.
Arteriosclerosis and Vascular Aging
VSMC dedifferentiation and migration contribute to arteriosclerosis. Kanglexin counters VSMC dedifferentiation and associated arteriosclerosis through inhibiting PDGFR, suggesting that PDGFR-driven migration is a driver of vascular aging. RBM24-mediated JAK2 stabilization also regulates VSMC phenotypic switching in vascular remodeling.
From vascular associated smooth muscle cell migration-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is gene X required for VSMC migration? | CRISPR knockout in primary VSMCs or A7r5 cells; scratch wound and Boyden chamber assays |
| Does a point mutation in gene X affect VSMC migration? | CRISPR point mutation knock-in in VSMCs; migration assays and signaling analysis |
| Does a disease-associated variant in gene X alter VSMC migration? | Knock-in of the variant in VSMCs; comparison with wild-type |
| Where is gene X expressed during VSMC migration? | Tagged knock-in (e.g., GFP) in VSMCs; live-cell imaging |
| Does overexpression of gene X enhance VSMC migration? | Lentiviral or CRISPR activation overexpression in VSMCs; migration assays |
| Can gene X be targeted to inhibit neointimal hyperplasia? | VSMC-specific knockout mouse; carotid artery ligation or wire injury model |
How to Study the vascular associated smooth muscle cell migration Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Scratch wound assay | Rate of cell migration into a denuded area | Screening genes or drugs affecting VSMC migration |
| Transwell migration assay | Number of cells migrating through a membrane | Quantifying chemotaxis toward PDGF or angiotensin II |
| Live-cell imaging | Dynamics of cytoskeleton and migration | Visualizing lamellipodia and focal adhesions |
| RNA-seq | Global transcriptome changes | Identifying pathways altered during VSMC migration |
| RIP/CLIP | RNA-protein interactions | Mapping RBM24 binding to JAK2 mRNA |
| Proteomics | Protein expression and modifications | Discovering novel regulators of VSMC migration |
| Metabolomics | Metabolic intermediates and fluxes | Detecting glycolytic reprogramming in VSMCs |
| Immunofluorescence | Protein localization and cytoskeletal structure | Assessing phenotypic switching markers |
In Vitro Migration Assays
Scratch wound healing and transwell (Boyden chamber) assays are standard methods to quantify VSMC migration. Cells are seeded in monolayers or on membranes, and migration is induced by chemoattractants such as PDGF-BB or angiotensin II. These assays are used to test the effects of gene knockout, knockdown, or overexpression on migratory capacity.
Live-Cell Imaging and Cytoskeletal Analysis
Live-cell imaging of fluorescently labeled VSMCs allows real-time visualization of lamellipodia dynamics, focal adhesion turnover, and cell polarity. Tagged knock-in of cytoskeletal proteins (e.g., actin-GFP) enables tracking of migration in vitro and in vivo. High-content imaging can quantify migration speed, directionality, and persistence.
Transcriptomics and RNA Interactomics
RNA sequencing (RNA-seq) of migrating VSMCs identifies differentially expressed genes and pathways. RNA immunoprecipitation (RIP) and crosslinking and immunoprecipitation (CLIP) can map RNA-protein interactions, such as RBM24 binding to JAK2 mRNA. Circular RNA profiling has revealed hsa_circ_0001402 as a regulator of VSMC migration.
Proteomics and Metabolomics
Mass spectrometry-based proteomics quantifies protein expression and post-translational modifications during VSMC migration. Metabolomics can detect metabolic shifts, such as increased glycolysis mediated by LONP1 in pulmonary artery smooth muscle cells. These approaches identify novel therapeutic targets and biomarkers.
How CRISPR Can Be Used to Study GO:1904738 vascular associated smooth muscle cell migration
Knockout
CRISPR knockout of candidate genes in VSMCs is used to determine loss-of-function effects on migration. For example, VSMC-specific deletion of ANGPTL8 in mice prevents angiotensin II-induced hypertension and cardiovascular hypertrophy, demonstrating a causal role in VSMC migration. In vitro, knockout of RBM24 or LONP1 reduces VSMC migration, validating their pro-migratory functions. Knockout models are essential for target validation.
Point Mutation
CRISPR point mutation knock-in introduces specific amino acid substitutions or disease-associated variants to test their impact on VSMC migration. For instance, mutating phosphorylation sites in PDGFR or JAK2 can reveal their importance in downstream signaling. Point mutation models help dissect molecular mechanisms without confounding effects of complete gene loss.
Knock-in
Knock-in of reporter genes (e.g., GFP, luciferase) or epitope tags allows visualization and quantification of VSMC migration in real time. Tagged knock-in of contractile proteins or signaling molecules can track their localization during migration. Knock-in of human disease variants into mouse VSMCs can model genetic contributions to vascular disease.
Overexpression
CRISPR activation (CRISPRa) or lentiviral overexpression is used to test gain-of-function effects on VSMC migration. Overexpression of hsa_circ_0001402 alleviates neointimal hyperplasia by regulating VSMC proliferation, migration, and autophagy, indicating a protective role. Overexpression of heme oxygenase-1 inhibits VSMC migration, supporting its therapeutic potential. These models complement knockout studies.
How EDITGENE Supports vascular associated smooth muscle cell migration Research
Researchers studying vascular associated smooth muscle cell migration-related genes often need to determine whether a candidate gene is causally involved in the migratory phenotype. EDITGENE provides a comprehensive suite of CRISPR-based cell model and screening services to accelerate this discovery process, from knockout to precise point mutations and overexpression.
Contact EDITGENE today to design your custom CRISPR model for vascular associated smooth muscle cell migration research.
Frequently Asked Questions About vascular associated smooth muscle cell migration
What is GO:1904738?
GO:1904738 is the Gene Ontology term for vascular associated smooth muscle cell migration, defined as the orderly movement of a vascular smooth muscle cell from one site to another.
What genes are involved in vascular smooth muscle cell migration?
Key genes include PDGFR, ANGPTL8, RBM24, JAK2, LONP1, MPC1, HMOX1, and non-coding RNAs such as hsa_circ_0001402 and miR-183-5p.
How is vascular smooth muscle cell migration measured?
Common methods include scratch wound healing, transwell migration assays, live-cell imaging, and high-content analysis.
Why is vascular smooth muscle cell migration important in disease?
Excessive VSMC migration contributes to atherosclerosis, restenosis, hypertension, and pulmonary hypertension.
What is the role of PDGFR in VSMC migration?
PDGFR activation by PDGF ligands drives VSMC dedifferentiation and migration, and its inhibition counters arteriosclerosis.
How does ANGPTL8 affect VSMC migration?
VSMC-specific deletion of ANGPTL8 prevents angiotensin II-promoted hypertension and cardiovascular hypertrophy, indicating a pro-migratory role.
Can CRISPR be used to study VSMC migration?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable causal testing of genes in VSMC migration.
What is the role of RBM24 in VSMC migration?
RBM24 stabilizes JAK2 mRNA and regulates VSMC phenotypic switching, thereby promoting migration and vascular remodeling.
How does LONP1 influence VSMC migration?
LONP1 degrades MPC1, facilitating glycolytic reprogramming and migration of pulmonary artery smooth muscle cells in pulmonary hypertension.
What services does EDITGENE offer for VSMC migration research?
EDITGENE provides CRISPR knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics services for vascular smooth muscle cell research.
Conclusion
Vascular associated smooth muscle cell migration (GO:1904738) is a fundamental biological process that underlies both normal vascular repair and devastating cardiovascular diseases. The integration of QuickGO definitions with verified PubMed literature reveals a complex regulatory network involving growth factor receptors, RNA-binding proteins, metabolic enzymes, and non-coding RNAs. Targeting these pathways holds promise for treating atherosclerosis, restenosis, hypertension, and pulmonary hypertension. CRISPR-based models are indispensable for causal validation of candidate genes, and EDITGENE offers comprehensive services to accelerate this research.
References
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- 3. Zhang H et al.. 2025. RBM24 regulates phenotypic switching of smooth muscle cell in vascular remodeling by stabilizing JAK2 mRNA.. Cardiovasc Res 121(17):2791-2808 PMID: 41216933
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