GO:0034105 positive regulation of tissue remodeling: Signaling Mechanisms, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0034105 (positive regulation of tissue remodeling) is a biological process term describing any process that activates or increases the frequency, rate, or extent of tissue remodeling.
• Tissue remodeling is a coordinated process involving extracellular matrix turnover, fibroblast activation, immune cell crosstalk, and metabolic reprogramming of vascular and cardiac cells [1,4,6].
• Key molecular drivers include CTHRC1-positive cardiac fibroblasts after myocardial infarction, CD23-mediated spleen-heart signaling, and hexokinase 2-driven glycolysis in pericytes [4,5,6].
• Epigenetic regulators such as METTL14 modulate vascular ageing and remodeling, linking RNA methylation to tissue remodeling control.
• Dysregulated positive regulation of tissue remodeling underlies cardiac hypertrophy, fibrosis, vascular abnormalities, and tumor-associated vascular remodeling [1,5,6].
• CRISPR knockout, point mutation, knock-in, and overexpression models are essential for causally testing candidate regulators of tissue remodeling in vitro and in vivo.
Description
GO:0034105, positive regulation of tissue remodeling, is a Gene Ontology biological process term defined as any process that activates or increases the frequency, rate, or extent of tissue remodeling. Tissue remodeling is a dynamic, multicellular process through which organs and tissues alter their architecture in response to physiological cues, injury, or pathological stress. This term captures the upstream and downstream signals that positively drive matrix deposition, cellular hypertrophy, fibroblast activation, and vascular restructuring [1,4]. Understanding positive regulation of tissue remodeling is critical because excessive or maladaptive remodeling contributes to heart failure, vascular disease, and tumor progression [1,5,6]. Researchers study this process to identify molecular switches that can be therapeutically targeted to promote adaptive repair or limit pathological fibrosis [4,6]. The term is ontology-based and agnostic to specific genes, but real literature has identified numerous regulators, including CTHRC1, METTL14, HK2, and CD23-related signaling components [2,4,5,6].
positive regulation of tissue remodeling At A Glance
| GO ID | GO:0034105 |
|---|---|
| GO term | positive regulation of tissue remodeling |
| Ontology | biological_process |
| Synonym | positive regulation of tissue remodelling |
| Definition | Any process that activates or increases the frequency, rate, or extent of tissue remodeling. |
| Major function | Upregulation of tissue remodeling processes, including extracellular matrix turnover, cellular hypertrophy, and fibroblast activation. |
| Related processes | Cardiac hypertrophy, vascular remodeling, fibrosis, wound healing, tumor microenvironment remodeling. |
| Key regulators | CTHRC1, METTL14, HK2, CD23, clusterin, and T cell homeostasis-related factors [2,4,5,6,7,8]. |
| Research relevance | Target for anti-fibrotic, cardio-protective, and anti-angiogenic therapies. |
What Is GO:0034105?
In our own words, GO:0034105 describes the set of biological activities that positively regulate tissue remodeling. It does not refer to a single gene or pathway but rather to any process that increases the frequency, rate, or extent of tissue remodeling. This includes signaling cascades, transcriptional programs, metabolic shifts, and cell-cell communication events that promote changes in tissue architecture, such as extracellular matrix reorganization, cell hypertrophy, and fibroblast activation [1,4,6].
Why Is positive regulation of tissue remodeling Important in Cell Biology?
Positive regulation of tissue remodeling is fundamentally important because it determines whether tissues adapt beneficially or succumb to pathological remodeling. In the heart, positive regulation of remodeling can lead to cardiac hypertrophy and fibrosis, which are major causes of heart failure [1,6]. In the vasculature, it contributes to vascular ageing and abnormal tumor blood vessel formation [2,5]. Understanding the positive regulators of tissue remodeling provides mechanistic insight into disease progression and identifies candidate targets for therapeutic intervention [4,6].
• Cardiac hypertrophy and heart failure: positive regulation of tissue remodeling drives maladaptive cardiac growth.
• Vascular ageing: epigenetic regulators such as METTL14 modulate vascular remodeling.
• Tumor angiogenesis: hexokinase 2-driven glycolysis in pericytes promotes abnormal tumor blood vessel remodeling.
• Myocardial infarction repair: CTHRC1-positive fibroblasts are crucial for post-infarction remodeling.
• Spleen-heart crosstalk: CD23-mediated signals promote cardiac remodeling.
• Fibrosis: excessive positive regulation leads to extracellular matrix deposition and organ dysfunction [7,8].
• Wound healing: controlled positive regulation is required for tissue repair.
• Therapeutic targeting: inhibitors of positive regulators may reduce pathological remodeling [4,6].
• Biomarker discovery: remodeling-related genes can serve as disease biomarkers.
• CRISPR modeling: enables causal testing of candidate regulators in disease models.
What Happens During positive regulation of tissue remodeling?
Initiation by injury or stress signals
In simple terms: When tissue is injured or stressed, cells release signals that start the remodeling process.
Positive regulation of tissue remodeling is often initiated by mechanical stress, ischemia, or inflammatory cytokines. In the heart, pressure overload triggers signaling cascades that activate cardiac hypertrophy programs. After myocardial infarction, damage-associated signals recruit immune cells and activate fibroblasts. These initiating events set the stage for downstream remodeling.
Activation of fibroblasts and matrix deposition
In simple terms: Fibroblasts become activated and produce new extracellular matrix proteins.
A central step in positive regulation of tissue remodeling is the activation of fibroblasts, particularly CTHRC1-positive cardiac fibroblasts after myocardial infarction, which are crucial for remodeling. These cells deposit collagens and other matrix components, altering tissue stiffness and architecture. Clusterin has also been implicated in the regulation of cardiac remodeling after transverse aortic constriction.
Immune cell crosstalk and signaling
In simple terms: Immune cells communicate with tissue cells to amplify remodeling signals.
Immune cells play a key role in positively regulating tissue remodeling. CD23-mediated spleen-heart cross-talk promotes cardiac remodeling. T cell homeostasis is also involved, as epigallocatechin gallate attenuates overload-induced cardiac ECM remodeling via restoring T cell homeostasis. These interactions amplify and sustain remodeling responses.
Metabolic reprogramming and vascular remodeling
In simple terms: Changes in cell metabolism can drive blood vessel remodeling.
Metabolic shifts, such as hexokinase 2-driven glycolysis in pericytes, activate contractility and lead to tumor blood vessel abnormalities. This demonstrates that positive regulation of tissue remodeling includes metabolic control of vascular cells. Similarly, deletion of METTL14, a methylation regulator, attenuates vascular ageing, linking RNA methylation to vascular remodeling.
Resolution or progression to pathology
In simple terms: Remodeling can either resolve or become chronic and pathological.
The outcome of positive regulation of tissue remodeling depends on context. Physiological remodeling can be adaptive, but sustained activation leads to pathological hypertrophy, fibrosis, and organ failure [1,6]. Understanding the balance between adaptive and maladaptive remodeling is a major research focus [4,7].
Key Genes Involved in GO:0034105 positive regulation of tissue remodeling
The following genes and proteins have been experimentally implicated in positive regulation of tissue remodeling, based on the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CTHRC1 | Cardiac fibroblast marker; promotes post-MI remodeling | Crucial for cardiac repair after myocardial infarction |
| METTL14 | RNA methylation regulator; modulates vascular ageing | Deletion attenuates vascular ageing |
| HK2 | Hexokinase 2; drives glycolysis in pericytes | Activates contractility and tumor blood vessel abnormalities |
| CD23 | Low-affinity IgE receptor; mediates spleen-heart signaling | Promotes cardiac remodeling |
| CLU | Clusterin; secreted chaperone | Regulated in heart after transverse aortic constriction |
| T cells | Immune cells; modulate ECM remodeling | T cell homeostasis affects cardiac ECM remodeling |
| MYH7 | Beta-myosin heavy chain; cardiac hypertrophy marker | Involved in physiological and pathological hypertrophy |
| NPPA | Atrial natriuretic peptide; hypertrophy marker | Upregulated in cardiac hypertrophy |
| NPPB | Brain natriuretic peptide; hypertrophy marker | Upregulated in cardiac hypertrophy |
| ACTA1 | Skeletal muscle actin; remodeling marker | Associated with tissue remodeling |
| COL1A1 | Collagen type I; ECM component | Deposited during fibrosis and remodeling [7,8] |
| COL3A1 | Collagen type III; ECM component | Deposited during fibrosis and remodeling [7,8] |
| FN1 | Fibronectin; ECM glycoprotein | Promotes remodeling and fibrosis |
| VEGFA | Vascular endothelial growth factor | Angiogenesis and vascular remodeling |
| TGFB1 | Transforming growth factor beta | Master regulator of fibrosis and remodeling [1,4] |
| IL6 | Interleukin 6; inflammatory cytokine | Promotes remodeling after injury |
| TNF | Tumor necrosis factor; inflammatory cytokine | Modulates cardiac remodeling |
| MMP9 | Matrix metalloproteinase 9 | Degrades ECM during remodeling |
How Is positive regulation of tissue remodeling Regulated?
Positive regulation of tissue remodeling is controlled at multiple levels. Transcriptional programs downstream of mechanical stress and cytokines drive hypertrophy and fibrosis. Epigenetic regulators such as METTL14 modulate vascular ageing through RNA methylation. Metabolic enzymes like hexokinase 2 link glycolysis to pericyte contractility and vascular remodeling. Immune signaling, including CD23-mediated spleen-heart crosstalk, provides systemic regulation. T cell homeostasis also influences ECM remodeling. These layers of regulation ensure that tissue remodeling is tightly controlled but can become dysregulated in disease.
positive regulation of tissue remodeling and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CTHRC1 | Myocardial infarction; cardiac fibrosis | Mouse MI model; Cthrc1 KO |
| METTL14 | Vascular ageing | Mettl14 KO mouse; vascular smooth muscle cells |
| HK2 | Tumor angiogenesis; vascular abnormalities | Hk2 KO; pericyte-specific deletion |
| CD23 | Cardiac remodeling; heart failure | Cd23 KO; spleen-heart axis models |
| CLU | Pressure overload; cardiac hypertrophy | Transverse aortic constriction; Clu KO |
Cardiac hypertrophy and heart failure
Positive regulation of tissue remodeling is central to cardiac hypertrophy, a major risk factor for heart failure. Mechanisms of physiological and pathological cardiac hypertrophy involve complex signaling that increases heart size and alters gene expression. CD23-mediated spleen-heart signaling promotes cardiac remodeling, suggesting a role for immune crosstalk in heart failure. Clusterin is regulated in the heart after transverse aortic constriction, a model of pressure overload.
Vascular ageing and tumor angiogenesis
Vascular remodeling is positively regulated by epigenetic and metabolic factors. Deletion of METTL14 attenuates vascular ageing, indicating that RNA methylation promotes vascular remodeling. In tumors, hexokinase 2-driven glycolysis in pericytes activates contractility and leads to abnormal blood vessel remodeling, contributing to tumor progression.
Myocardial infarction and fibrosis
After myocardial infarction, CTHRC1-positive cardiac fibroblasts are crucial for remodeling and repair. Excessive fibroblast activation can lead to fibrosis, and T cell homeostasis modulates overload-induced cardiac ECM remodeling. These findings highlight the dual nature of positive regulation of tissue remodeling in repair versus pathology.
From positive regulation of tissue remodeling-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is CTHRC1 required for post-MI remodeling? | CTHRC1 knockout mouse |
| Does METTL14 deletion attenuate vascular ageing? | METTL14 knockout mouse |
| Does HK2-driven glycolysis in pericytes promote tumor vessel abnormalities? | HK2 conditional knockout in pericytes |
| Does CD23 signaling mediate spleen-heart crosstalk? | CD23 knockout mouse |
| Is clusterin regulated after pressure overload? | Transverse aortic constriction in mice |
| Does T cell homeostasis affect cardiac ECM remodeling? | T cell reconstitution models |
How to Study the positive regulation of tissue remodeling Process
| Method | What It Measures | Typical Application |
|---|---|---|
| scRNA-seq | Cell-type-specific gene expression | Identify fibroblast subsets in remodeling |
| Histology | Tissue architecture and fibrosis | Assess cardiac remodeling [1,7] |
| Echocardiography | Cardiac function and hypertrophy | Monitor heart remodeling in vivo |
| Metabolic flux assay | Glycolysis and oxidative phosphorylation | Measure HK2-driven metabolism |
| MeRIP-seq | RNA methylation sites | Study METTL14 in vascular ageing |
| Flow cytometry | Immune cell populations | Analyze T cell homeostasis |
| Western blot | Protein expression | Detect clusterin and ECM proteins |
| Immunofluorescence | Protein localization | Visualize CTHRC1+ fibroblasts |
Single-cell RNA sequencing
Single-cell RNA sequencing has been used to identify CTHRC1-positive cardiac fibroblasts after myocardial infarction, revealing a crucial role in remodeling. This method allows unbiased discovery of cell populations driving positive regulation of tissue remodeling.
Histology and imaging
Histological staining for collagen and imaging of tissue architecture are standard methods to assess remodeling. For example, cardiac fibrosis and hypertrophy are evaluated by Masson's trichrome and echocardiography [1,7].
Metabolic assays
Glycolysis and metabolic flux assays can measure hexokinase 2 activity in pericytes, linking metabolism to vascular remodeling. Seahorse analysis and lactate production are commonly used.
Epigenetic profiling
RNA methylation and epigenetic marks can be profiled by MeRIP-seq and related techniques to study METTL14 function in vascular ageing.
How CRISPR Can Be Used to Study GO:0034105 positive regulation of tissue remodeling
Knockout
CRISPR knockout of candidate genes such as CTHRC1, METTL14, or HK2 can test their requirement for positive regulation of tissue remodeling. For example, Mettl14 knockout attenuates vascular ageing, and Hk2 deletion affects pericyte contractility.
Point Mutation
Point mutations can dissect specific residues required for signaling. For instance, mutating phosphorylation sites in CD23 or HK2 could reveal their role in remodeling [5,6].
Knock-in
Knock-in of reporter genes or tagged alleles allows tracking of remodeling cells. A CTHRC1-GFP knock-in would enable visualization of activated fibroblasts after MI.
Overexpression
Overexpression of positive regulators such as CTHRC1 or HK2 can drive excessive remodeling, modeling pathological states [4,5]. This is useful for gain-of-function studies.
How EDITGENE Supports positive regulation of tissue remodeling Research
Researchers studying positive regulation of tissue remodeling-related genes often need to determine whether a candidate gene is causally involved in driving or sustaining remodeling. EDITGENE provides CRISPR-based cell models and screening services to enable such causal studies.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of tissue remodeling research.
Frequently Asked Questions About positive regulation of tissue remodeling
What is GO:0034105?
GO:0034105 is the Gene Ontology term for positive regulation of tissue remodeling, defined as any process that activates or increases the frequency, rate, or extent of tissue remodeling.
What genes are involved in positive regulation of tissue remodeling?
Key genes include CTHRC1, METTL14, HK2, CD23, and CLU, as shown in recent studies [2,4,5,6,7].
How is tissue remodeling positively regulated?
It is regulated by injury signals, fibroblast activation, immune crosstalk, metabolic reprogramming, and epigenetic changes [1,4,5,6].
What diseases involve positive regulation of tissue remodeling?
Cardiac hypertrophy, heart failure, vascular ageing, tumor angiogenesis, and fibrosis [1,2,5,6].
What is the role of CTHRC1 in tissue remodeling?
CTHRC1-positive cardiac fibroblasts are crucial for remodeling after myocardial infarction.
How does METTL14 affect vascular remodeling?
Deletion of METTL14 attenuates vascular ageing, indicating it positively regulates vascular remodeling.
What is the role of HK2 in tumor blood vessels?
Hexokinase 2-driven glycolysis in pericytes activates contractility and leads to tumor blood vessel abnormalities.
How can CRISPR be used to study tissue remodeling?
CRISPR knockout, point mutation, knock-in, and overexpression models can test causal roles of candidate genes in remodeling [2,4,5].
What methods are used to study positive regulation of tissue remodeling?
scRNA-seq, histology, echocardiography, metabolic assays, and epigenetic profiling [1,2,4,5,7].
Why is positive regulation of tissue remodeling important?
It determines whether tissues adapt or undergo pathological changes, and it is a therapeutic target for heart and vascular diseases [1,6].
Conclusion
GO:0034105 positive regulation of tissue remodeling is a critical biological process that governs tissue adaptation and pathology. Research has identified diverse molecular regulators, from CTHRC1-positive fibroblasts to METTL14-dependent epigenetic control and HK2-driven metabolism [2,4,5]. Understanding these mechanisms offers opportunities for therapeutic intervention in cardiac, vascular, and fibrotic diseases. CRISPR-based models are indispensable for causally testing these regulators and accelerating translation.
References
- 1. Nakamura M et al.. 2018. Mechanisms of physiological and pathological cardiac hypertrophy.. Nat Rev Cardiol 15(7):387-407 PMID: 29674714
- 2. Liu X et al.. 2025. Deletion of METTL14, a key methylation regulator, attenuates vascular ageing.. Eur Heart J 46(45):4953-4968 PMID: 40758401
- 4. Ruiz-Villalba A et al.. 2020. Single-Cell RNA Sequencing Analysis Reveals a Crucial Role for CTHRC1 (Collagen Triple Helix Repeat Containing 1) Cardiac Fibroblasts After Myocardial Infarction.. Circulation 142(19):1831-1847 PMID: 32972203
- 5. Meng YM et al.. 2021. Hexokinase 2-driven glycolysis in pericytes activates their contractility leading to tumor blood vessel abnormalities.. Nat Commun 12(1):6011 PMID: 34650057
- 6. Feng Y et al.. 2025. Spleen-Heart Cross-Talk Through CD23-Mediated Signal Promotes Cardiac Remodeling.. Circ Res 137(1):83-102 PMID: 40391441
- 7. Turkieh A et al.. 2024. Regulation of Clusterin in the Heart and Plasma of Mice After Transverse Aortic Constriction.. J Cell Mol Med 28(23):e70290 PMID: 39671261
- 8. Han Y et al.. 2017. Epigallocatechin gallate attenuates overload‑induced cardiac ECM remodeling via restoring T cell homeostasis.. Mol Med Rep 16(3):3542-3550 PMID: 28713936
