GO:0014895 smooth muscle hypertrophy: Cellular Growth Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0014895 smooth muscle hypertrophy describes the enlargement of smooth muscle cells without cell division, a process distinct from hyperplasia.
• It occurs physiologically in the uterus during pregnancy and pathologically in hypertension, asthma, and intestinal disorders.
• Key molecular drivers include angiotensin II, PGF2alpha, CXCL12, and angiopoietin-like protein 8 (ANGPTL8).
• Hypertrophy involves increased protein synthesis, cytoskeletal remodeling, and altered contractile protein expression.
• Animal models such as angiotensin II-infused mice and CXCL12-ablated mice are used to study vascular and cardiac hypertrophy.
• CRISPR-based knockout, knock-in, and overexpression models enable causal gene validation in smooth muscle hypertrophy research.
Description
Smooth muscle hypertrophy (GO:0014895) is a biological process defined as the enlargement or overgrowth of an organ due to an increase in the size of its smooth muscle cells without cell division. This process is distinct from hyperplasia, which involves an increase in cell number. Physiological hypertrophy is a normal developmental process and can also occur in mature structures on demand, such as the uterus during pregnancy. Pathological smooth muscle hypertrophy contributes to diseases including hypertension, asthma, and intestinal obstruction. Understanding the molecular mechanisms underlying smooth muscle hypertrophy is critical for developing targeted therapies for these conditions. This article synthesizes authoritative QuickGO data and verified PubMed literature to provide a comprehensive overview of the genes, functions, and research methods associated with GO:0014895.
smooth muscle hypertrophy At A Glance
| GO ID | GO:0014895 |
|---|---|
| GO term | smooth muscle hypertrophy |
| Ontology | biological_process |
| Synonym | none |
| Major function | Increase in smooth muscle cell size without cell division, leading to organ enlargement |
| Physiological example | Uterine smooth muscle hypertrophy during pregnancy |
| Pathological examples | Vascular hypertrophy in hypertension, airway remodeling in asthma, intestinal hypertrophy |
| Key molecular drivers | Angiotensin II, PGF2alpha, CXCL12, ANGPTL8 |
| Distinction | Hypertrophy (cell size increase) vs. hyperplasia (cell number increase) |
What Is GO:0014895?
GO:0014895 smooth muscle hypertrophy is defined as the enlargement or overgrowth of all or part of an organ due to an increase in size of its smooth muscle cells without cell division. Physiological hypertrophy is a normal process during development and can also occur in mature structures on demand. In the uterus, smooth muscle cells undergo hypertrophy during pregnancy.
Why Is smooth muscle hypertrophy Important in Cell Biology?
Smooth muscle hypertrophy is a fundamental biological process with significant implications for human health and disease. It is essential for normal physiological functions such as uterine expansion during pregnancy and adaptive responses to increased workload in hollow organs. However, dysregulated smooth muscle hypertrophy contributes to the pathogenesis of major diseases, including hypertension, atherosclerosis, asthma, and gastrointestinal disorders. Understanding the molecular and cellular mechanisms of smooth muscle hypertrophy is therefore crucial for identifying therapeutic targets and developing interventions to prevent or reverse pathological remodeling.
• Physiological role in uterine expansion during pregnancy.
• Pathological vascular hypertrophy in hypertension and cardiovascular disease.
• Airway smooth muscle hypertrophy in asthma contributes to airway obstruction.
• Intestinal smooth muscle hypertrophy can lead to obstruction and motility disorders.
• Involvement of angiotensin II and PGF2alpha signaling pathways.
• CXCL12/CXCR7 axis implicated in coronary artery development and cardiac hypertrophy.
• ANGPTL8 as a potential therapeutic target for hypertension and cardiovascular hypertrophy.
• Model organisms including mice, pigeons, and chickens used to study smooth muscle hypertrophy.
• CRISPR gene editing enables causal validation of candidate genes in hypertrophy models.
• Bioinformatics and omics approaches reveal novel regulators of smooth muscle hypertrophy.
What Happens During smooth muscle hypertrophy?
Initiation by Mechanical and Humoral Stimuli
In simple terms: Smooth muscle cells start to grow when they receive signals like stretch or hormones.
Smooth muscle hypertrophy is initiated by mechanical stretch, hormonal signals, and growth factors. In the uterus, pregnancy-related hormones and stretch trigger hypertrophy. In blood vessels, angiotensin II promotes vascular smooth muscle cell hypertrophy, as shown in mice with smooth muscle-specific deletion of angiopoietin-like protein 8 (ANGPTL8), which prevents angiotensin II-induced hypertension and cardiovascular hypertrophy. PGF2alpha also induces hypertrophy of vascular smooth muscle cells through specific molecular mechanisms.
Increased Protein Synthesis and Cell Size
In simple terms: The cell makes more proteins and structural components, causing it to enlarge.
Once initiated, smooth muscle hypertrophy involves a substantial increase in protein synthesis, leading to cell enlargement without DNA replication or cell division. This is accompanied by increased expression of contractile proteins and cytoskeletal elements. Different types of smooth muscle hypertrophy have been described, with variations in the extent of protein synthesis and organelle biogenesis.
Cytoskeletal and Contractile Protein Remodeling
In simple terms: The cell's internal skeleton and contractile machinery are reorganized to accommodate the larger size.
Hypertrophic smooth muscle cells undergo remodeling of their cytoskeleton and contractile apparatus. This includes changes in the expression and organization of actin, myosin, and associated proteins. In airway smooth muscle, growth in asthma involves proliferation, hypertrophy, and migration, with hypertrophy contributing to increased muscle mass. The molecular mechanisms underlying PGF2alpha-induced hypertrophy of vascular smooth muscle cells involve specific signaling pathways that alter contractile protein expression.
Organ-Level Consequences
In simple terms: The enlarged cells cause the whole organ to grow or thicken.
At the organ level, smooth muscle hypertrophy leads to thickening of the smooth muscle layer in hollow organs. In the uterus, this results in the massive expansion required for pregnancy. In the intestine, smooth muscle hypertrophy can cause obstruction, as seen in cases of intestinal smooth muscle hypertrophy/hyperplasia in pigeons and chickens. Generalized smooth muscle hypertrophy is a rare condition that can affect multiple organs.
Key Genes Involved in GO:0014895 smooth muscle hypertrophy
The following genes and proteins have been implicated in smooth muscle hypertrophy based on verified PubMed literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ANGPTL8 | Promotes angiotensin II-induced hypertension and cardiovascular hypertrophy | Smooth muscle-specific deletion prevents hypertrophy in mice |
| CXCL12 | Chemokine involved in coronary artery development and cardiac hypertrophy | Smooth muscle-specific ablation causes defective coronary arteries and cardiac hypertrophy |
| CXCR7 | Receptor for CXCL12, downregulated upon CXCL12 ablation | Associated with defective coronary arteries and cardiac hypertrophy |
| PGF2alpha | Prostaglandin that induces vascular smooth muscle cell hypertrophy | Molecular mechanisms studied in vascular smooth muscle cells |
| Angiotensin II | Hormone that promotes vascular smooth muscle hypertrophy | Used to induce hypertension and cardiovascular hypertrophy in models |
| Myosin | Contractile protein increased during hypertrophy | Marker of smooth muscle hypertrophy |
| Actin | Cytoskeletal protein involved in hypertrophy | Remodeling during smooth muscle growth |
| Elastin | Extracellular matrix protein affected in hypertrophy | Altered in intestinal smooth muscle hypertrophy |
| Collagen | Extracellular matrix component | Deposition changes in hypertrophic smooth muscle |
| mTOR | Kinase regulating protein synthesis | Potential mediator of hypertrophic growth |
| Calcineurin | Phosphatase involved in hypertrophic signaling | Implicated in smooth muscle hypertrophy |
| NFAT | Transcription factor downstream of calcineurin | Regulates hypertrophic gene expression |
| GATA6 | Transcription factor | Potential role in smooth muscle hypertrophy |
| SRF | Serum response factor | Regulates smooth muscle contractile genes |
| MYOCD | Myocardin | Coactivator of SRF in smooth muscle |
| miR-143/145 | MicroRNAs regulating smooth muscle phenotype | Potential role in hypertrophy |
| KLF4 | Kruppel-like factor 4 | Modulates smooth muscle phenotype |
| TGF-beta | Growth factor | Promotes smooth muscle hypertrophy |
How Is smooth muscle hypertrophy Regulated?
Smooth muscle hypertrophy is regulated by a complex network of signaling pathways. Angiotensin II is a key regulator, as its effects are mediated through ANGPTL8 in vascular smooth muscle cells. PGF2alpha signaling also induces hypertrophy through specific molecular mechanisms. The CXCL12/CXCR7 axis is critical for coronary artery development, and its disruption leads to cardiac hypertrophy. Additionally, mechanical stretch and hormonal changes during pregnancy regulate uterine smooth muscle hypertrophy. Different types of smooth muscle hypertrophy exist, suggesting context-dependent regulatory mechanisms.
smooth muscle hypertrophy and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ANGPTL8 | Hypertension and cardiovascular hypertrophy | Smooth muscle-specific knockout mice |
| CXCL12 | Defective coronary arteries and cardiac hypertrophy | Smooth muscle-specific knockout mice |
| PGF2alpha | Vascular smooth muscle hypertrophy | In vitro cell culture |
| CXCR7 | Coronary artery defects and cardiac hypertrophy | Knockout or knockdown models |
| Angiotensin II | Hypertension and cardiovascular hypertrophy | Angiotensin II-infused mice |
Hypertension and Cardiovascular Hypertrophy
Vascular smooth muscle hypertrophy is a hallmark of hypertension and contributes to cardiovascular remodeling. Angiotensin II promotes hypertension and cardiovascular hypertrophy through ANGPTL8, and smooth muscle-specific deletion of ANGPTL8 prevents these effects in mice. This highlights ANGPTL8 as a potential therapeutic target for hypertension and associated cardiovascular hypertrophy.
Asthma and Airway Remodeling
Airway smooth muscle hypertrophy is a key feature of airway remodeling in asthma. The growth of airway smooth muscle involves proliferation, hypertrophy, and migration, all of which contribute to increased muscle mass and airway obstruction. Understanding these processes is essential for developing therapies that target airway remodeling.
Intestinal Smooth Muscle Hypertrophy
Intestinal smooth muscle hypertrophy can occur in various conditions, including obstruction and motility disorders. Cases of intestinal smooth muscle hypertrophy/hyperplasia have been documented in pigeons and chickens, providing animal models for studying the condition. Generalized smooth muscle hypertrophy is a rare disorder that can affect multiple organs.
Cardiac Hypertrophy and Coronary Artery Defects
Smooth muscle-specific ablation of CXCL12 in mice leads to downregulation of CXCR7, defective coronary arteries, and cardiac hypertrophy. This demonstrates the critical role of smooth muscle-derived CXCL12 in coronary artery development and cardiac homeostasis.
From smooth muscle hypertrophy-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does ANGPTL8 in smooth muscle cells mediate angiotensin II-induced hypertension? | Smooth muscle-specific ANGPTL8 knockout mice |
| What is the role of CXCL12 in coronary artery development and cardiac hypertrophy? | Smooth muscle-specific CXCL12 knockout mice |
| How does PGF2alpha induce vascular smooth muscle cell hypertrophy? | In vitro vascular smooth muscle cell culture with PGF2alpha treatment |
| What are the mechanisms of uterine smooth muscle hypertrophy during pregnancy? | Pregnant animal models and uterine smooth muscle cells |
| How does airway smooth muscle hypertrophy contribute to asthma? | Asthma animal models and airway smooth muscle cells |
| What genes are essential for intestinal smooth muscle hypertrophy? | Intestinal smooth muscle hypertrophy models in pigeons and chickens |
How to Study the smooth muscle hypertrophy Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Histology (H&E, immunohistochemistry) | Cell size and tissue morphology | Detection of smooth muscle hypertrophy in tissues |
| Western blot | Protein expression levels | Quantification of contractile proteins and signaling molecules |
| qRT-PCR | mRNA expression | Analysis of gene expression changes during hypertrophy |
| RNA sequencing | Transcriptome-wide expression | Identification of novel genes involved in hypertrophy |
| In situ hybridization | Localization of mRNA | Detection of specific gene expression in smooth muscle layers |
| Electron microscopy | Ultrastructural changes | Visualization of organelles and cytoskeleton in hypertrophic cells |
| Cell culture with hypertrophic stimuli | Cellular responses | Mechanistic studies of hypertrophy in vitro |
| Genetic knockout models | Causal role of genes | In vivo validation of gene function in hypertrophy |
Histological and Imaging Techniques
Histological analysis using hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence can visualize smooth muscle hypertrophy in tissue sections. These methods allow measurement of smooth muscle cell size and layer thickness.
Molecular and Biochemical Assays
Western blotting, quantitative PCR, and RNA sequencing can quantify expression of contractile proteins, growth factors, and signaling molecules during hypertrophy. These techniques help identify molecular changes associated with smooth muscle hypertrophy.
Genetic and Pharmacological Interventions
Knockout and transgenic mouse models, as well as pharmacological inhibitors, are used to dissect signaling pathways. For example, angiotensin II infusion and ANGPTL8 deletion have been used to study vascular hypertrophy.
In Vitro Cell Culture Models
Primary smooth muscle cells and cell lines can be stimulated with hypertrophic agents such as PGF2alpha or angiotensin II to study molecular mechanisms in a controlled environment.
How CRISPR Can Be Used to Study GO:0014895 smooth muscle hypertrophy
Knockout
CRISPR knockout of candidate genes such as ANGPTL8 or CXCL12 in smooth muscle cells can validate their causal role in hypertrophy. For example, smooth muscle-specific ANGPTL8 knockout prevents angiotensin II-induced hypertension and cardiovascular hypertrophy in mice.
Point Mutation
Introducing point mutations in genes like CXCR7 or PGF2alpha receptors can help dissect specific signaling domains required for hypertrophy. This approach allows precise structure-function analysis.
Knock-in
Knock-in of reporter genes or epitope tags into endogenous loci such as ANGPTL8 or CXCL12 enables real-time tracking of protein expression and localization during hypertrophy.
Overexpression
Overexpression of pro-hypertrophic genes like angiotensin II or PGF2alpha in smooth muscle cells can induce hypertrophy and mimic pathological conditions, providing gain-of-function models.
How EDITGENE Supports smooth muscle hypertrophy Research
Researchers studying smooth muscle hypertrophy-related genes often need to determine whether a candidate gene is causally involved in the initiation or progression of hypertrophic growth. EDITGENE provides comprehensive CRISPR gene editing services to support such investigations, from knockout and point mutation to knock-in and overexpression models.
Contact EDITGENE today to design your custom CRISPR model for smooth muscle hypertrophy research.
Frequently Asked Questions About smooth muscle hypertrophy
What is smooth muscle hypertrophy?
Smooth muscle hypertrophy (GO:0014895) is the enlargement or overgrowth of an organ due to an increase in the size of its smooth muscle cells without cell division.
What genes are involved in smooth muscle hypertrophy?
Key genes include ANGPTL8, CXCL12, CXCR7, and PGF2alpha, as well as angiotensin II signaling components.
How does smooth muscle hypertrophy differ from hyperplasia?
Hypertrophy involves an increase in cell size without cell division, while hyperplasia involves an increase in cell number.
What diseases are associated with smooth muscle hypertrophy?
Hypertension, asthma, intestinal obstruction, and cardiac hypertrophy are associated with smooth muscle hypertrophy.
What are the molecular mechanisms of smooth muscle hypertrophy?
Mechanisms include increased protein synthesis, cytoskeletal remodeling, and activation of signaling pathways such as angiotensin II and PGF2alpha.
How is smooth muscle hypertrophy studied in the lab?
Common methods include histological analysis, Western blotting, RNA sequencing, and genetic mouse models.
What is the role of ANGPTL8 in smooth muscle hypertrophy?
ANGPTL8 in vascular smooth muscle cells promotes angiotensin II-induced hypertension and cardiovascular hypertrophy; its deletion prevents these effects.
What is the role of CXCL12 in smooth muscle hypertrophy?
Smooth muscle-specific ablation of CXCL12 leads to defective coronary arteries and cardiac hypertrophy.
Can CRISPR be used to study smooth muscle hypertrophy?
Yes, CRISPR knockout, knock-in, and overexpression models can validate gene function in smooth muscle hypertrophy.
What model organisms are used to study smooth muscle hypertrophy?
Mice, pigeons, and chickens are used as models for smooth muscle hypertrophy.
Conclusion
Smooth muscle hypertrophy (GO:0014895) is a critical biological process with essential physiological roles and significant pathological implications. Research using animal models and CRISPR gene editing has identified key molecular drivers such as ANGPTL8, CXCL12, and PGF2alpha. Continued investigation into the mechanisms of smooth muscle hypertrophy will inform therapeutic strategies for hypertension, asthma, and other related disorders. EDITGENE provides comprehensive CRISPR services to support these research efforts.
References
- 1. Jiao X et al.. 2023. Vascular smooth muscle cells specific deletion of angiopoietin-like protein 8 prevents angiotensin II-promoted hypertension and cardiovascular hypertrophy.. Cardiovasc Res 119(9):1856-1868 PMID: 37285486
- 2. Gabella G. 1990. Hypertrophy of visceral smooth muscle.. Anat Embryol (Berl) 182(5):409-24 PMID: 2291488
- 3. Bentley JK et al.. 2008. Airway smooth muscle growth in asthma: proliferation, hypertrophy, and migration.. Proc Am Thorac Soc 5(1):89-96 PMID: 18094090
- 4. Johansson B. 1984. Different types of smooth muscle hypertrophy.. Hypertension 6(6 Pt 2):III64-8 PMID: 6394492
- 5. da Silva AL et al.. 1992. Generalized smooth muscle hypertrophy.. Rev Paul Med 110(4):180-2 PMID: 1341009
- 6. Ghadge SK et al.. 2021. Smooth Muscle Specific Ablation of CXCL12 in Mice Downregulates CXCR7 Associated with Defective Coronary Arteries and Cardiac Hypertrophy.. Int J Mol Sci 22(11) PMID: 34072818
- 7. Pavone S et al.. 2019. Cases of intestinal smooth muscle hypertrophy/hyperplasia in pigeon and chickens.. J Vet Med Sci 81(9):1351-1354 PMID: 31366815
- 8. Fan C et al.. 2010. Molecular mechanisms underlying PGF2alpha-induced hypertrophy of vascular smooth muscle cells.. Yakugaku Zasshi 130(2):211-4 PMID: 20118645
