GO:0140149 non-collagenous component of interstitial matrix: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0140149 describes the non-collagenous protein and glycoprotein fraction of interstitial extracellular matrix, including fibronectin and elastin.
• This compartment excludes collagen but is essential for matrix assembly, cell adhesion, and tissue biomechanics.
• Key non-collagenous interstitial matrix proteins include fibronectin, elastin, laminin, and other glycoproteins detected in fibrosis and aging.
• Dysregulation of non-collagenous interstitial matrix components is linked to liver fibrosis, cirrhosis, Parkinson's disease, and tumor progression.
• CRISPR knockout, knock-in, and overexpression models enable causal testing of individual matrix genes in relevant cell types.
• Proteomics, glycomics, and immunoelectron microscopy are established methods for localizing and quantifying these matrix components.
Description
The extracellular matrix (ECM) is a complex network of proteins and glycoproteins that provides structural support and biochemical signals to cells. Within the ECM, the interstitial matrix is distinguished from basement membranes by its composition and tissue distribution. GO:0140149, non-collagenous component of interstitial matrix, defines the proteinaceous fraction of the interstitial matrix that excludes collagen, encompassing glycoproteins such as fibronectin and elastin. This term is critical for researchers because non-collagenous matrix components mediate cell-matrix interactions, regulate growth factor availability, and contribute to tissue remodeling in development and disease. Unlike collagenous components, which dominate tensile strength, non-collagenous interstitial matrix proteins provide elasticity, adhesive cues, and signaling functions. Fibronectin, for example, is a multifunctional glycoprotein that assembles into fibrillar networks and binds integrins, while elastin confers reversible extensibility to tissues such as lung, skin, and arteries. These proteins are synthesized by fibroblasts, endothelial cells, and other mesenchymal cells and are deposited into the interstitial space where they form supramolecular assemblies. Understanding GO:0140149 is essential for dissecting mechanisms of fibrosis, cancer progression, and neurodegeneration. For instance, biochemical markers of liver fibrosis include extracellular components such as fibronectin and laminin, which are elevated in cirrhosis. In Parkinson's disease, glycomics and proteomics studies have revealed altered matrix protein profiles in the brain. Thus, this GO term provides a framework for investigating how non-collagenous interstitial matrix components contribute to physiology and pathology.
non-collagenous component of interstitial matrix At A Glance
| GO ID | GO:0140149 |
|---|---|
| GO term | non-collagenous component of interstitial matrix |
| Ontology | cellular_component |
| Synonym | None |
| Major function | Provides non-collagenous structural and signaling glycoproteins (e.g., fibronectin, elastin) in the interstitial matrix |
| Key components | Fibronectin, elastin, laminin, and other glycoproteins |
| Cellular sources | Fibroblasts, endothelial cells, and other mesenchymal cells |
| Associated diseases | Liver fibrosis, cirrhosis, Parkinson's disease, and tumor progression |
| Research methods | Proteomics, glycomics, immunoelectron microscopy, and CRISPR editing |
What Is GO:0140149?
GO:0140149 (non-collagenous component of interstitial matrix) is a cellular component term describing the portion of the interstitial extracellular matrix that does not contain collagen. It includes glycoproteins such as fibronectin and elastin, which are secreted and assembled into the interstitial space to provide structural and signaling functions.
Why Is non-collagenous component of interstitial matrix Important in Cell Biology?
GO:0140149 is important because non-collagenous interstitial matrix components are not merely passive structural elements; they actively regulate cell behavior, tissue homeostasis, and disease progression. Fibronectin and elastin, for example, control cell adhesion, migration, and mechanical properties of tissues. Alterations in these components are hallmarks of fibrosis, where excessive deposition of non-collagenous matrix proteins contributes to organ dysfunction. In cancer, tumor-derived matrix proteins influence invasion and metastasis. In neurodegeneration, matrix remodeling may affect neuronal survival and regeneration. Therefore, studying this compartment is essential for understanding both normal physiology and pathological states.
• Non-collagenous interstitial matrix proteins provide structural integrity and elasticity to tissues.
• They mediate cell adhesion and signaling through interactions with integrins and growth factors.
• Fibronectin and elastin are key biomarkers in liver fibrosis and cirrhosis.
• Altered matrix composition is observed in Parkinson's disease brain.
• Tumor cells synthesize non-collagenous matrix components that promote invasion.
• Laminin, a non-collagenous glycoprotein, is critical for nerve regeneration.
• These components are synthesized by endothelial cells and fibroblasts.
• They are targets for anti-fibrotic and anti-cancer therapies.
• CRISPR models enable functional dissection of individual matrix genes.
• Proteomic and glycomic profiling reveals disease-specific matrix signatures.
What Happens During non-collagenous component of interstitial matrix?
Synthesis and Secretion of Non-Collagenous Matrix Proteins
In simple terms: Cells produce and release matrix proteins outside themselves.
Non-collagenous interstitial matrix components are synthesized in the endoplasmic reticulum and Golgi apparatus of fibroblasts, endothelial cells, and other mesenchymal cells. For example, bovine retinal endothelial cells biosynthesize extracellular matrix components including fibronectin and laminin. Similarly, a human tumor cell line produces type IV procollagen and other basement membrane proteins, indicating that non-collagenous matrix proteins are secreted by diverse cell types. These proteins are then secreted into the extracellular space where they assemble into supramolecular structures.
Assembly and Crosslinking of Fibronectin and Elastin
In simple terms: Secreted proteins link together to form a stable network.
Once secreted, fibronectin molecules self-assemble into fibrils through interactions with integrins and other matrix proteins. Elastin is deposited onto microfibrils and crosslinked by lysyl oxidase to form elastic fibers. These assembly processes are critical for the mechanical properties of interstitial tissues. In liver fibrosis, excessive deposition of fibronectin and other non-collagenous components contributes to scar formation.
Interaction with Cells and Signaling
In simple terms: Matrix proteins talk to cells to control their behavior.
Non-collagenous matrix proteins bind to cell surface receptors such as integrins, transmitting signals that regulate proliferation, migration, and differentiation. Fibronectin, for instance, contains RGD motifs that interact with integrins. Laminin, another non-collagenous glycoprotein, is localized in normal and regenerating mouse sciatic nerve, where it supports Schwann cell function and axonal regeneration. These interactions are essential for tissue repair and homeostasis.
Remodeling and Turnover
In simple terms: The matrix is constantly built up and broken down.
The non-collagenous interstitial matrix is dynamically remodeled by matrix metalloproteinases (MMPs) and other proteases. This turnover is tightly regulated in normal tissues but becomes dysregulated in fibrosis and cancer. In Parkinson's disease, altered glycomics and proteomics of brain matrix suggest changes in remodeling processes. Understanding these dynamics is key to developing therapies that target matrix deposition.
Key Genes Involved in GO:0140149 non-collagenous component of interstitial matrix
The following genes encode major non-collagenous interstitial matrix proteins and related modifying enzymes, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| FN1 | Encodes fibronectin, a key adhesive glycoprotein | Central to matrix assembly and cell adhesion; elevated in fibrosis |
| ELN | Encodes elastin, provides elasticity | Critical for lung, skin, and vascular function; mutations cause elastinopathies |
| LAMA1 | Encodes laminin subunit alpha-1 | Component of basement membranes and interstitial matrix in some tissues |
| LAMB1 | Encodes laminin subunit beta-1 | Involved in cell adhesion and migration |
| LAMC1 | Encodes laminin subunit gamma-1 | Essential for basement membrane assembly |
| COL4A1 | Encodes type IV collagen alpha-1 | Although collagenous, it is co-expressed with non-collagenous components |
| COL4A2 | Encodes type IV collagen alpha-2 | Co-secreted with non-collagenous matrix proteins |
| LOX | Lysyl oxidase, crosslinks elastin and collagen | Regulates matrix stiffness; implicated in fibrosis and cancer |
| MMP2 | Matrix metalloproteinase-2, degrades matrix | Remodeling enzyme; altered in fibrosis and neurodegeneration |
| MMP9 | Matrix metalloproteinase-9, degrades matrix | Involved in matrix turnover and inflammation |
| TGFB1 | Transforming growth factor beta-1, induces matrix synthesis | Master regulator of fibrosis; drives non-collagenous matrix deposition |
| FBN1 | Fibrillin-1, microfibril component | Scaffold for elastin deposition; mutations cause Marfan syndrome |
| SPARC | Secreted protein acidic and rich in cysteine | Modulates matrix assembly and cell-matrix interactions |
| THBS1 | Thrombospondin-1, matricellular protein | Regulates cell adhesion and angiogenesis |
| TNC | Tenascin-C, matricellular protein | Expressed during development and in tumors |
| POSTN | Periostin, matricellular protein | Promotes fibrosis and tumor progression |
| VIM | Vimentin, intermediate filament | Not a matrix protein but marks mesenchymal cells producing matrix |
| ACTA2 | Alpha-smooth muscle actin | Marks myofibroblasts that synthesize matrix |
How Is non-collagenous component of interstitial matrix Regulated?
The synthesis and assembly of non-collagenous interstitial matrix components are regulated by growth factors and cytokines, notably TGFB1, which induces fibronectin and elastin expression in fibroblasts and other cells. Matrix metalloproteinases (MMPs) such as MMP2 and MMP9 degrade these components, maintaining a balance between deposition and turnover. In liver fibrosis, this balance is disrupted, leading to excessive accumulation of non-collagenous matrix proteins. Additionally, post-translational modifications such as glycosylation influence matrix protein function and stability, as revealed by glycomics studies in Parkinson's disease brain.
non-collagenous component of interstitial matrix and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| FN1 | Liver fibrosis, cirrhosis | Knockout in hepatic stellate cells; overexpression in fibroblasts |
| ELN | Elastinopathies, vascular disease | Knock-in of patient mutations in iPSC-derived smooth muscle cells |
| LAMA1 | Neurodegeneration, nerve regeneration | Knockout in Schwann cells; tagged knock-in for localization |
| MMP2 | Fibrosis, cancer invasion | Point mutation to disable catalytic activity; overexpression |
| TGFB1 | Fibrosis, cancer | Knockout in fibroblasts; inducible overexpression in liver |
Liver Fibrosis and Cirrhosis
Liver fibrosis is characterized by excessive deposition of extracellular matrix components, including non-collagenous proteins such as fibronectin and laminin. Biochemical markers of liver fibrosis include these extracellular components, which are elevated in cirrhosis. The accumulation of non-collagenous interstitial matrix proteins contributes to scar formation and loss of liver function. Targeting these components may offer therapeutic strategies for fibrosis.
Parkinson's Disease and Neurodegeneration
Glycomics and proteomics studies of human brain have revealed altered extracellular matrix profiles in Parkinson's disease, including changes in non-collagenous matrix components. These alterations may affect neuronal survival and synaptic function. Laminin, a non-collagenous glycoprotein, is localized in regenerating mouse sciatic nerve, suggesting a role in nerve repair. Understanding matrix changes in neurodegeneration could lead to new biomarkers or therapies.
Cancer and Tumor Microenvironment
Tumor cells often synthesize and remodel non-collagenous interstitial matrix components to promote invasion and metastasis. A human tumor cell line has been shown to biosynthesize type IV procollagen and other basement membrane proteins, indicating active matrix production. Fibronectin and tenascin-C are overexpressed in many cancers and correlate with poor prognosis. Targeting these matrix proteins or their receptors is an active area of cancer research.
From non-collagenous component of interstitial matrix-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of FN1 reduce matrix assembly? | FN1 knockout in fibroblasts or hepatic stellate cells |
| How does a point mutation in ELN affect elastic fiber formation? | ELN point-mutation knock-in in iPSCs |
| Can tagged laminin track matrix dynamics? | LAMA1 knock-in with fluorescent tag in neurons |
| Does overexpression of TGFB1 drive fibrosis? | TGFB1 overexpression in mouse liver |
| What is the role of MMP2 in matrix turnover? | MMP2 knockout or catalytically dead mutant in cancer cells |
| Does fibronectin glycosylation change in Parkinson's disease? | Glycomics and proteomics of patient-derived brain tissue |
How to Study the non-collagenous component of interstitial matrix Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Proteomics | Protein composition and abundance | Profiling matrix proteins in disease tissues |
| Glycomics | Glycan structures on matrix proteins | Detecting glycosylation changes in Parkinson's disease |
| Immunoelectron microscopy | Ultrastructural localization of matrix proteins | Visualizing laminin in nerve regeneration |
| CRISPR knockout | Loss-of-function effects on matrix assembly | Testing FN1 or ELN function in fibroblasts |
| CRISPR knock-in | Tagged or mutant protein expression | Tracking laminin dynamics in neurons |
| ELISA | Quantification of specific matrix proteins | Measuring fibronectin in liver fibrosis |
| Western blot | Protein expression levels | Validating matrix protein changes in cell models |
| qPCR | mRNA expression of matrix genes | Assessing transcriptional regulation by TGFB1 |
Proteomics and Glycomics
Mass spectrometry-based proteomics and glycomics enable comprehensive profiling of non-collagenous interstitial matrix components in tissues and cell cultures. These methods have been used to identify altered matrix proteins in Parkinson's disease brain. They are essential for discovering disease-specific matrix signatures and potential biomarkers.
Immunoelectron Microscopy
Immunoelectron microscopy allows ultrastructural localization of matrix proteins such as laminin in normal and regenerating tissues. This technique provides high-resolution spatial information about matrix assembly and distribution, which is critical for understanding how non-collagenous components organize in the interstitial space.
CRISPR-Cas9 Genome Editing
CRISPR-Cas9 knockout, knock-in, and point mutation strategies enable functional dissection of individual matrix genes. For example, knocking out FN1 or ELN in relevant cell types can reveal their roles in matrix assembly and cell behavior. These models are indispensable for causal inference in matrix biology.
Biochemical Assays for Matrix Components
Biochemical markers of liver fibrosis include extracellular components such as fibronectin and laminin, which can be quantified by ELISA or Western blot. Such assays are used to assess matrix deposition in patient samples and experimental models, providing quantitative readouts of disease progression.
How CRISPR Can Be Used to Study GO:0140149 non-collagenous component of interstitial matrix
Knockout
CRISPR knockout of genes encoding non-collagenous interstitial matrix proteins, such as FN1 or ELN, allows researchers to determine their essential roles in matrix assembly and cell adhesion. For example, knocking out FN1 in fibroblasts can reveal defects in fibrillogenesis and cell migration. These models are valuable for identifying which components are required for tissue homeostasis.
Point Mutation
Point mutations can be introduced into matrix genes to model human disease variants or to disable specific functional domains. For instance, mutating the RGD motif in FN1 can disrupt integrin binding without affecting protein secretion. Such precision models help dissect structure-function relationships in non-collagenous matrix proteins.
Knock-in
Knock-in of fluorescent or epitope tags into endogenous matrix genes enables real-time tracking of protein localization and dynamics. Tagging LAMA1 in neurons can reveal how laminin is deposited and remodeled during nerve regeneration. This approach is powerful for studying matrix assembly in live cells and tissues.
Overexpression
Overexpression of matrix genes, such as TGFB1 or FN1, can drive excessive matrix deposition and model fibrotic or tumorigenic states. For example, overexpressing TGFB1 in mouse liver induces fibrosis with increased non-collagenous matrix components. These models are useful for testing anti-fibrotic therapies.
How EDITGENE Supports non-collagenous component of interstitial matrix Research
Researchers studying non-collagenous component of interstitial matrix-related genes often need to determine whether a candidate gene is causally involved in matrix assembly, disease progression, or treatment response. EDITGENE provides a comprehensive suite of CRISPR-based services to accelerate this discovery process.
Contact EDITGENE today to design your custom CRISPR model for non-collagenous component of interstitial matrix research.
Frequently Asked Questions About non-collagenous component of interstitial matrix
What is GO:0140149?
GO:0140149 is a Gene Ontology cellular component term describing the non-collagenous component of interstitial extracellular matrices, including glycoproteins like fibronectin and elastin.
What genes are involved in non-collagenous component of interstitial matrix?
Key genes include FN1 (fibronectin), ELN (elastin), LAMA1, LAMB1, LAMC1 (laminins), and modifying enzymes such as LOX and MMPs.
What diseases are associated with non-collagenous interstitial matrix?
Diseases include liver fibrosis, cirrhosis, Parkinson's disease, and cancer progression.
How is the non-collagenous interstitial matrix studied?
Common methods include proteomics, glycomics, immunoelectron microscopy, and CRISPR-based gene editing.
What is the difference between collagenous and non-collagenous interstitial matrix?
Collagenous components provide tensile strength, while non-collagenous components like fibronectin and elastin provide elasticity, adhesion, and signaling functions.
Which cells produce non-collagenous interstitial matrix proteins?
Fibroblasts, endothelial cells, and other mesenchymal cells synthesize these proteins.
Can CRISPR be used to study non-collagenous matrix genes?
Yes, CRISPR knockout, knock-in, and overexpression models enable functional studies of matrix genes in relevant cell types.
What is the role of fibronectin in the interstitial matrix?
Fibronectin is a multifunctional glycoprotein that assembles into fibrils, binds integrins, and regulates cell adhesion and migration.
How does elastin contribute to tissue function?
Elastin provides reversible elasticity to tissues such as lung, skin, and arteries, and is crosslinked by lysyl oxidase.
What biomarkers indicate liver fibrosis related to non-collagenous matrix?
Elevated levels of fibronectin and laminin are biochemical markers of liver fibrosis and cirrhosis.
Conclusion
GO:0140149, non-collagenous component of interstitial matrix, represents a vital compartment of the extracellular matrix that extends beyond structural support to actively regulate cell behavior and tissue homeostasis. Its components, including fibronectin, elastin, and laminins, are implicated in fibrosis, neurodegeneration, and cancer. Understanding the synthesis, assembly, and regulation of these proteins is essential for developing targeted therapies. CRISPR-based models and advanced proteomic methods provide powerful tools to dissect the roles of individual matrix genes, paving the way for new discoveries in matrix biology and disease treatment.
References
- 1. Abbate M et al.. 1989. [Nephrology].. Medicina (Firenze) 9(4):467-74 PMID: 2699352
- 2. Bolarin DM et al.. 2007. Biochemical markers, extracellular components in liver fibrosis and cirrhosis.. Nig Q J Hosp Med 17(1):42-52 PMID: 17688172
- 3. Raghunathan R et al.. 2020. A glycomics and proteomics study of aging and Parkinson's disease in human brain.. Sci Rep 10(1):12804 PMID: 32733076
- 4. Alitalo K et al.. 1980. Biosynthesis of two subunits of type IV procollagen and of other basement membrane proteins by a human tumor cell line.. Eur J Biochem 109(1):247-55 PMID: 6250836
- 5. Canfield AE et al.. 1986. The biosynthesis of extracellular-matrix components by bovine retinal endothelial cells displaying distinctive morphological phenotypes.. Biochem J 235(2):375-83 PMID: 3741397
- 7. Kuecherer-Ehret A et al.. 1990. Immunoelectron microscopic localization of laminin in normal and regenerating mouse sciatic nerve.. J Neurocytol 19(1):101-9 PMID: 2351991
