GO:1905609 positive regulation of smooth muscle cell-matrix adhesion: Signaling, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1905609 describes any process that activates or increases the frequency, rate or extent of smooth muscle cell-matrix adhesion, a biological process critical for vascular remodeling and tissue repair [1,4].
• Smooth muscle cell-matrix adhesion is dynamically regulated by matricellular proteins such as thrombospondin-1 and CD147, which modulate integrin signaling and extracellular matrix remodeling [2,5,6].
• Key molecular players include integrins, cadherin-11, drebrin, and ERK1/2-dependent chemotaxis pathways that converge on actin cytoskeleton reorganization [4,6,7].
• Dysregulation of this process contributes to atherosclerosis, aortic remodeling, peritoneal injury, and valve myofibroblast mechanobiology [2,4,5,7].
• Single-cell transcriptomics has revealed distinct smooth muscle cell populations in human peripheral veins that differentially express matrix adhesion genes.
• CRISPR-based knockout, knock-in, and overexpression models enable causal interrogation of genes regulating smooth muscle cell-matrix adhesion for therapeutic target discovery [4,7].
Description
Smooth muscle cells (SMCs) are essential for the contractile and synthetic functions of hollow organs, including blood vessels, airways, and the gastrointestinal tract. Their ability to adhere to and remodel the surrounding extracellular matrix (ECM) is fundamental to vascular development, wound healing, and tissue homeostasis [1,4]. The Gene Ontology term GO:1905609, positive regulation of smooth muscle cell-matrix adhesion, captures the biological processes that enhance the frequency, rate, or extent of this adhesion. This term is increasingly relevant to researchers studying vascular pathology, fibrosis, and cancer stroma, where SMC-ECM interactions drive disease progression [2,5]. Mechanistically, positive regulation of SMC-matrix adhesion involves integrin activation, matricellular protein signaling, and cytoskeletal reorganization. For example, thrombospondin-1 promotes SMC chemotaxis through ERK1/2-dependent pathways, thereby enhancing adhesion to matrix components. CD147 (basigin) expression in peritoneal injury models correlates with increased matrix adhesion and fibrosis. Drebrin, an actin-binding protein, regulates angiotensin II-induced aortic remodeling by modulating SMC adhesion dynamics. These findings underscore the importance of precise regulation for vascular health. Understanding GO:1905609 is critical for developing targeted therapies against atherosclerosis, restenosis, and organ fibrosis. Advanced tools such as single-cell transcriptomics and CRISPR gene editing now allow researchers to dissect the causal roles of specific genes in this process [8,7]. This article synthesizes current knowledge on the mechanisms, key genes, disease relevance, and research methods for studying positive regulation of smooth muscle cell-matrix adhesion.
positive regulation of smooth muscle cell-matrix adhesion At A Glance
| GO ID | GO:1905609 |
|---|---|
| GO term | positive regulation of smooth muscle cell-matrix adhesion |
| Ontology | biological_process |
| Synonym | activation of smooth muscle cell-matrix adhesion; up regulation of smooth muscle cell-matrix adhesion; up-regulation of smooth muscle cell-matrix adhesion; upregulation of smooth muscle cell-matrix adhesion |
| Major function | Enhances the attachment of smooth muscle cells to extracellular matrix components, promoting vascular remodeling, tissue repair, and pathological fibrosis [1,4,5]. |
| Related cellular component | Focal adhesions, integrin complexes, actin cytoskeleton [4,7] |
| Related molecular function | Integrin binding, extracellular matrix binding, kinase activity (e.g., ERK1/2) |
| Key regulators | Thrombospondin-1, CD147, drebrin, cadherin-11, angiotensin II [4,5,6,7] |
| Disease relevance | Atherosclerosis, aortic remodeling, peritoneal injury, valve disease [2,4,5,7] |
What Is GO:1905609?
GO:1905609 is a biological process term defined as any process that activates or increases the frequency, rate or extent of smooth muscle cell-matrix adhesion. In simpler terms, it encompasses all molecular events that strengthen or promote the attachment of smooth muscle cells to the extracellular matrix, including signaling cascades, integrin activation, and cytoskeletal rearrangements that stabilize cell-matrix contacts [1,4].
Why Is positive regulation of smooth muscle cell-matrix adhesion Important in Cell Biology?
Positive regulation of smooth muscle cell-matrix adhesion is a central mechanism in vascular biology and pathology. It governs how SMCs respond to mechanical and biochemical cues from the ECM, influencing processes such as neointima formation, plaque stability, and fibrosis [2,4]. Dysregulation leads to excessive matrix deposition, arterial stiffening, and organ failure, making this process a prime target for therapeutic intervention in cardiovascular and fibrotic diseases [5,7].
• Critical for vascular remodeling and repair after injury [1,4].
• Drives atherosclerotic plaque progression and stability.
• Mediates peritoneal fibrosis and injury responses.
• Regulates valve myofibroblast mechanobiology in heart valve disease.
• Involved in angiotensin II-induced aortic remodeling and hypertension.
• Modulates SMC chemotaxis and migration via ERK1/2 signaling.
• Contributes to tissue-specific SMC heterogeneity in human veins.
• Provides targets for anti-fibrotic and anti-atherosclerotic therapies [2,5].
• Enables mechanistic studies using CRISPR knockout and knock-in models [4,7].
• Links ECM stiffness to gene expression through mechanotransduction.
What Happens During positive regulation of smooth muscle cell-matrix adhesion?
Initiation by Matricellular Proteins and Growth Factors
In simple terms: Signals from the matrix or growth factors start the process.
Positive regulation of SMC-matrix adhesion is often initiated by matricellular proteins such as thrombospondin-1, which binds to integrins and activates intracellular signaling. Angiotensin II also triggers adhesion through G-protein coupled receptor pathways, leading to drebrin phosphorylation and actin remodeling. CD147 expression in peritoneal injury models promotes matrix adhesion and fibrosis.
Integrin Activation and Focal Adhesion Assembly
In simple terms: Integrins switch to a high-affinity state and cluster to form focal adhesions.
Integrins are the primary transmembrane receptors for ECM proteins. Upon activation, they cluster at focal adhesions, recruiting adaptor proteins such as talin, paxillin, and vinculin. Cadherin-11 regulates valve myofibroblast mechanobiology by modulating integrin-mediated adhesion. This step is essential for transmitting mechanical forces and activating downstream kinases [4,7].
Cytoskeletal Reorganization and Contractility
In simple terms: The cell's internal skeleton rearranges to strengthen attachment.
Actin stress fiber formation and myosin light chain phosphorylation increase tension at adhesion sites. Drebrin, an actin-binding protein, regulates angiotensin II-induced aortic remodeling by stabilizing actin filaments. ERK1/2 signaling downstream of thrombospondin-1 promotes SMC chemotaxis and adhesion.
ECM Remodeling and Feedback
In simple terms: Cells modify the matrix, which feeds back to enhance adhesion.
SMCs secrete and remodel ECM components such as collagen and fibronectin. Matricellular proteins like CD147 and thrombospondin-1 modulate this remodeling [2,5]. In atherosclerosis, excessive matrix deposition and SMC adhesion contribute to plaque stability and stenosis. Single-cell studies reveal distinct SMC populations with varying matrix adhesion gene expression in human veins.
Key Genes Involved in GO:1905609 positive regulation of smooth muscle cell-matrix adhesion
The following genes and proteins have been experimentally implicated in the positive regulation of smooth muscle cell-matrix adhesion, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| THBS1 | Encodes thrombospondin-1; promotes SMC chemotaxis via ERK1/2 | Regulates adhesion and migration in vascular injury |
| BSG (CD147) | Matrix metalloproteinase inducer; enhances adhesion in peritoneal injury | Biomarker and target in fibrosis |
| DBN1 (Drebrin) | Actin-binding protein; stabilizes cytoskeleton during aortic remodeling | Mediates angiotensin II-induced adhesion |
| CDH11 | Cadherin-11; regulates valve myofibroblast mechanobiology | Target in heart valve disease |
| ITGB1 | Integrin beta-1; primary ECM receptor | Central to focal adhesion assembly [4,7] |
| ITGA5 | Integrin alpha-5; fibronectin receptor | Modulates SMC adhesion to fibronectin |
| FN1 | Fibronectin; ECM ligand for integrins | Substrate for SMC adhesion |
| COL1A1 | Collagen type I; major ECM component | Remodeled during atherosclerosis |
| MMP2 | Matrix metalloproteinase-2; degrades ECM | Regulates matrix turnover and adhesion |
| MMP9 | Matrix metalloproteinase-9; degrades ECM | Involved in SMC migration |
| ERK1/2 (MAPK3/MAPK1) | Kinases downstream of thrombospondin-1 | Required for SMC chemotaxis |
| AGTR1 | Angiotensin II receptor type 1 | Mediates angiotensin II-induced remodeling |
| TGFB1 | Transforming growth factor beta-1; promotes matrix synthesis | Drives fibrosis and adhesion |
| CTNNB1 | Beta-catenin; links adhesion to gene expression | Modulates SMC phenotype |
| VCL | Vinculin; focal adhesion protein | Structural component of adhesions |
| TLN1 | Talin-1; integrin activator | Essential for adhesion assembly |
| PXN | Paxillin; focal adhesion adaptor | Scaffold for signaling |
How Is positive regulation of smooth muscle cell-matrix adhesion Regulated?
Positive regulation of smooth muscle cell-matrix adhesion is controlled by a network of signaling pathways. Angiotensin II via AGTR1 activates drebrin and actin remodeling. Thrombospondin-1 signals through ERK1/2 to promote chemotaxis and adhesion. CD147 expression is upregulated in peritoneal injury and correlates with fibrosis. Matricellular proteins such as TGF-beta and CTGF modulate ECM synthesis and integrin affinity. Mechanical forces from ECM stiffness also feed back to enhance adhesion through cadherin-11 and beta-catenin. These pathways are potential targets for therapeutic modulation.
positive regulation of smooth muscle cell-matrix adhesion and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| THBS1 | Atherosclerosis, restenosis | Knockout mouse; SMC-specific overexpression |
| BSG (CD147) | Peritoneal fibrosis | Conditional knockout; CD147 inhibitor treatment |
| DBN1 | Aortic remodeling, hypertension | Drebrin knockout; angiotensin II infusion model |
| CDH11 | Heart valve disease | Cadherin-11 knockout; valve interstitial cell culture |
| ITGB1 | Vascular injury, fibrosis | SMC-specific integrin beta-1 knockout |
Atherosclerosis and Vascular Remodeling
In atherosclerosis, SMC-matrix adhesion contributes to fibrous cap formation and plaque stability. Matricellular proteins like thrombospondin-1 and CD147 are upregulated, promoting SMC migration and matrix deposition [2,5]. Drebrin regulates angiotensin II-induced aortic remodeling, linking adhesion to hypertension. Targeting these pathways may stabilize plaques or prevent restenosis.
Peritoneal Injury and Fibrosis
CD147 expression is elevated in peritoneal injury models, where it enhances SMC-matrix adhesion and fibrosis. This process is relevant to peritoneal dialysis complications and abdominal adhesions. Modulating CD147 or downstream integrins could reduce fibrotic outcomes.
Heart Valve Disease
Cadherin-11 regulates valve myofibroblast mechanobiology, affecting matrix adhesion and valve remodeling. Dysregulation leads to myxomatous degeneration and calcification. Targeting cadherin-11 may offer therapeutic benefit in valve disease.
Venous Remodeling and Single-Cell Heterogeneity
Single-cell transcriptomics of human peripheral veins revealed distinct SMC populations with differential expression of matrix adhesion genes. This heterogeneity may underlie variable responses to injury and disease, highlighting the need for personalized approaches.
From positive regulation of smooth muscle cell-matrix adhesion-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X promote SMC-matrix adhesion? | CRISPR knockout in primary SMCs followed by adhesion assay |
| Does point mutation in gene Y alter adhesion? | CRISPR point mutation knock-in in SMC cell line |
| Does overexpression of gene Z enhance adhesion? | Lentiviral overexpression in SMCs |
| Does tagged protein localize to focal adhesions? | CRISPR knock-in of fluorescent tag |
| Does gene W regulate adhesion in vivo? | SMC-specific conditional knockout mouse |
| Does gene V affect matrix remodeling? | CRISPR library screening in SMCs under adhesion conditions |
How to Study the positive regulation of smooth muscle cell-matrix adhesion Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Adhesion assay | Number of adherent cells | Screening genes affecting SMC-matrix adhesion |
| Immunofluorescence | Focal adhesion size and number | Validating cytoskeletal changes [4,7] |
| Single-cell RNA-seq | Gene expression heterogeneity | Identifying SMC subpopulations |
| Phosphoproteomics | Kinase activation | Mapping signaling pathways |
| CRISPR knockout | Loss-of-function effects | Causal gene validation |
| CRISPR knock-in | Tagged protein localization | Live-cell imaging of adhesion |
| Overexpression | Gain-of-function effects | Testing sufficiency of a gene |
| ECM stiffness assay | Mechanotransduction | Studying matrix feedback |
Adhesion Assays
In vitro adhesion assays measure SMC attachment to ECM proteins such as fibronectin or collagen. Cells are seeded on coated plates, washed, and adherent cells quantified by colorimetric or fluorescent methods. This is the primary functional readout for GO:1905609 [6,7].
Imaging of Focal Adhesions
Immunofluorescence for paxillin, vinculin, or talin visualizes focal adhesion number and size. Live-cell imaging of GFP-tagged integrins or actin allows dynamic assessment of adhesion turnover [4,7].
Transcriptomics and Single-Cell RNA-seq
RNA-seq and scRNA-seq identify genes differentially expressed during SMC-matrix adhesion. Single-cell studies of human veins revealed distinct SMC populations with varying adhesion gene signatures.
Proteomics and Phosphoproteomics
Mass spectrometry-based proteomics quantifies focal adhesion composition and signaling changes. Phosphoproteomics identifies kinases such as ERK1/2 activated during adhesion.
How CRISPR Can Be Used to Study GO:1905609 positive regulation of smooth muscle cell-matrix adhesion
Knockout
CRISPR knockout of candidate genes such as THBS1, BSG, or DBN1 in SMCs can abolish or reduce matrix adhesion, establishing necessity. Pooled knockout screens with adhesion-based selection identify novel regulators [4,6].
Point Mutation
Point mutations in integrin or kinase domains can dissect specific phosphorylation sites or binding interfaces. For example, mutating ERK1/2 phosphorylation sites in drebrin may reveal its role in adhesion [4,6].
Knock-in
Knock-in of fluorescent tags (e.g., GFP) into endogenous loci allows real-time tracking of focal adhesion proteins. Tagged knock-in of CDH11 or ITGB1 enables live-cell imaging of adhesion dynamics.
Overexpression
CRISPR activation (CRISPRa) or lentiviral overexpression of genes like CD147 or thrombospondin-1 can test sufficiency in promoting SMC-matrix adhesion and fibrosis [5,6].
How EDITGENE Supports positive regulation of smooth muscle cell-matrix adhesion Research
Researchers studying positive regulation of smooth muscle cell-matrix adhesion-related genes often need to determine whether a candidate gene is causally involved in adhesion, matrix remodeling, or disease progression. EDITGENE provides end-to-end CRISPR solutions to accelerate this discovery.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of smooth muscle cell-matrix adhesion research.
Frequently Asked Questions About positive regulation of smooth muscle cell-matrix adhesion
What is GO:1905609?
GO:1905609 is a Gene Ontology biological process term defined as any process that activates or increases the frequency, rate or extent of smooth muscle cell-matrix adhesion.
What genes are involved in positive regulation of smooth muscle cell-matrix adhesion?
Key genes include THBS1, BSG (CD147), DBN1 (drebrin), CDH11, ITGB1, and MAPK1/3 (ERK1/2), among others [4,5,6,7].
How is smooth muscle cell-matrix adhesion regulated?
It is regulated by matricellular proteins, integrin activation, growth factors like angiotensin II and TGF-beta, and mechanical forces from the ECM [2,4,6].
What diseases are associated with smooth muscle cell-matrix adhesion?
Atherosclerosis, aortic remodeling, peritoneal fibrosis, and heart valve disease are linked to dysregulated SMC-matrix adhesion [2,4,5,7].
What experimental methods study SMC-matrix adhesion?
Adhesion assays, immunofluorescence, single-cell RNA-seq, phosphoproteomics, and CRISPR screens are commonly used [6,7,8].
How does thrombospondin-1 regulate SMC adhesion?
Thrombospondin-1 promotes SMC chemotaxis through ERK1/2-dependent signaling, enhancing adhesion to matrix components.
What is the role of CD147 in peritoneal injury?
CD147 expression is elevated in peritoneal injury and correlates with increased matrix adhesion and fibrosis.
How does drebrin affect aortic remodeling?
Drebrin regulates angiotensin II-induced aortic remodeling by stabilizing actin filaments and modulating SMC adhesion.
Can CRISPR be used to study SMC-matrix adhesion?
Yes, CRISPR knockout, knock-in, and overexpression models enable causal interrogation of genes regulating this process [4,7].
What is the clinical relevance of GO:1905609?
Targeting positive regulation of SMC-matrix adhesion may treat atherosclerosis, fibrosis, and valve disease by reducing pathological matrix deposition [2,5,7].
Conclusion
Positive regulation of smooth muscle cell-matrix adhesion (GO:1905609) is a fundamental biological process with broad implications for vascular biology and disease. Key molecular players such as thrombospondin-1, CD147, drebrin, and cadherin-11 orchestrate adhesion through integrin signaling and cytoskeletal remodeling [4,5,6,7]. Dysregulation contributes to atherosclerosis, fibrosis, and valve disease, making this process a promising therapeutic target [2,5,7]. Advanced CRISPR tools and multi-omics approaches now allow researchers to dissect the causal roles of specific genes in SMC-matrix adhesion. EDITGENE offers comprehensive services to accelerate this research, from knockout and knock-in models to library screening and bioinformatics.
References
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- 2. Pervaiz N et al.. 2023. Matricellular proteins in atherosclerosis development.. Matrix Biol 120:1-23 PMID: 37086928
- 4. Zhang L et al.. 2018. Drebrin regulates angiotensin II-induced aortic remodelling.. Cardiovasc Res 114(13):1806-1815 PMID: 29931051
- 5. Seeger H et al.. 2017. CD147 expression in peritoneal injury.. Clin Exp Nephrol 21(6):1097-1104 PMID: 28551820
- 6. Gahtan V et al.. 1999. Thrombospondin-1 regulation of smooth muscle cell chemotaxis is extracellular signal-regulated protein kinases 1/2 dependent.. Surgery 126(2):203-7 PMID: 10455885
- 7. Bowler MA et al.. 2018. Cadherin-11 as a regulator of valve myofibroblast mechanobiology.. Am J Physiol Heart Circ Physiol 315(6):H1614-H1626 PMID: 30359089
- 8. Rojas MG et al.. 2024. The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis.. PLoS One 19(1):e0296264 PMID: 38206912
