Description

Product Description

Endotrophin (Mus musculus) (CAS 1678414-54-4) is a cleavage product of collagen type VI (COL6), specifically derived from the C-terminal C5 domain of the α3(VI) chain (COL6A3). This bioactive peptide fragment plays a crucial role as a fibrosis-inducing and inflammation-promoting signaling molecule in various pathological contexts, including adipose tissue dysfunction, liver fibrosis, cancer progression, and metabolic syndromes.

Collagen VI is a key extracellular matrix (ECM) protein found in most connective tissues, where it provides structural integrity and mechanical support. During tissue remodeling, proteolytic cleavage of COL6A3 releases endotrophin, which acts as a signaling mediator between the ECM and surrounding cells. Unlike structural collagen domains, endotrophin functions as a paracrine signaling peptide, actively modulating cellular communication and inflammatory pathways.

Origin and Molecular Nature

Endotrophin was first identified as a biologically active cleavage product released during ECM remodeling in adipose tissue. Its discovery linked ECM dynamics to inflammation and fibrosis, especially in the context of obesity-induced metabolic dysfunction. Endotrophin originates from the C-terminal Kunitz-like domain of COL6A3 and retains distinct structural motifs responsible for binding to integrins and growth factor receptors.

In mouse models, endotrophin expression increases in response to tissue stress, hypoxia, and metabolic dysregulation, particularly in adipocytes and fibroblasts. It has been shown to accumulate in fibrotic lesions, tumor stroma, and adipose depots, indicating its involvement in microenvironmental reprogramming.

Biological Functions and Pathophysiological Role

Endotrophin is not merely a degradation product; it is an active matricryptin — a bioactive ECM fragment that regulates cell signaling. It serves as a molecular link between ECM remodeling and cellular activation, participating in the following biological processes:

• Fibrosis Induction: Endotrophin triggers fibroblast-to-myofibroblast transition, promoting excessive collagen synthesis and tissue stiffening.

• Inflammation Enhancement: It induces cytokine and chemokine expression, leading to macrophage infiltration and sustained inflammatory signaling.

• Epithelial-Mesenchymal Transition (EMT): Endotrophin promotes EMT in epithelial and cancer cells, facilitating migration and invasion.

• Angiogenesis Modulation: It enhances endothelial proliferation and capillary formation through pro-angiogenic signaling.

• Metabolic Dysregulation: In adipose tissue, it contributes to insulin resistance, adipocyte dysfunction, and fibrosis under obesity-related conditions.

The pleiotropic effects of endotrophin make it a central mediator of tissue pathology, linking metabolic imbalance to chronic inflamma.

Role in Adipose Tissue and Metabolic Diseases

Endotrophin has been extensively studied in obesity and type 2 diabetes models. Elevated endotrophin levels in adipose tissue correlate with insulin resistance, macrophage accumulation, and ECM deposition. It acts through TGF-β signaling pathways to upregulate collagen I, fibr, promoting fibrosis and tissue rigidity.

Adipocyte-derived endotrophin exerts para on immune cells, enhancing macrophage polarization toward a pro-inflammatory (M1-like) phenotype. These events contribute to chronic low-gr characteristic of metabolic disorders. Neutralization of endotrophin via antibodies or genetic suppression has been shown to improve glucose tolerance, reduce fibrosis, and restore insulin sensitivity in animal models, positioning endotrophin as a therapeutic target in metabolic research.

Endotrophin and Cancer Microenvironment

In oncology, endotrophin plays a dual role as both a tumor-promoting factor and a stromal remodeling agent. Tumors often display elevated endotrophin levels, particularly in hypoxic regions rich in fibrotic stroma. Endotrophin enhances tumor cell motility, angiogenesis, and chemoresistance, facilitating metastasis. It stimulates TGF-β and PDGF signaling, which activate stromal fibroblasts and support tumor growth.

Additionally, endotrophin enhances epithelial-to-mesenchymal transition (EMT) in carcinoma cells, promoting invasiveness. Studies show that blocking endotrophin can reduce tumor growth and metastasis, making it a potential anti-cancer target in tumor stroma research.

Endotrophin as a Biomarker

Circulating endotrophin levels are emerging as a non-invasive biomarker for several diseases:

• Metabolic syndrome and insulin resistance

• Liver and kidney fibrosis

• Cardiac remodeling

• Cancer prognosis

Serum endotrophin concentrations correlate with disease severity and response to antifibrotic therapies, providing diagnostic and prognostic insights in both preclinical and clinical studies.

Research Applications

• Fibrosis and ECM remodeling studies

• Adipose tissue and obesity research

• Inflammatory and immune cell interaction assays

• Cancer stroma and EMT analysis

• Biomarker validation in metabolic or fibrotic diseases

Product Specifications

Synonyms

• Collagen VI α3 chain cleavage fragment

• Endotrophin peptide

• COL6A3-derived matricryptin

• Collagen VI C5 domain peptide

Mechanism of Action

Endotrophin acts as a matricryptin, a bioactive ECM-derived signaling fragment released from collagen VI during tissue remodeling. It binds to cell surface receptors such as integrins (αvβ3, αvβ5) and growth factor receptors (TGF-βR, PDGFR) to trigger downstream fibrotic and inflammatory signaling pathways.

Upon receptor engagement, endotrophin activates:

• TGF-β/SMAD pathway → induction of fibrotic gene expression (COL1A1, FN1, ACTA2).

• NF-κB pathway → upregulation of pro-inflammatory cytokines (IL-6, TNF-α, MCP-1).

• PI3K/AKT and MAPK signaling → promotion of fibroblast proliferation and migration.

In adipose tissue, endotrophin drives a feed-forward loop between fibroblast activation and macrophage recruitment. It enhances local ECM deposition and inflammatory infiltration, exacerbating tissue dysfunction. In tumors, it supports angiogenesis, immune evasion, and stromal expansion, thereby reshaping the tumor microenvironment.

Endotrophin’s biological activity illustrates the concept of ECM fragments as signaling molecules—not passive degradation products, but potent modulators of cellular crosstalk and disease progression.

Side Effects / Safety Notes

is provided strictly for research use only. It has no approved therapeutic application. In laboratory models, endotrophin overexpression can induce fibrosis and inflammatory responses; researchers should handle it with standard biosafety practices (BSL-2 or equivalent). Avoid inhalation or contact with skin and eyes.

There are no known toxic effects associated with in vitro use under normal research concentrations. However, due to its bioactivity, care should be taken to prevent unintended biological exposure.

Disclaimer

This product is intended for laboratory research purposes only. It must not be used in human or veterinary medicine, clinical diagnostics, or food processing. The information provided is for scientific communication and educational use. Compliance with institutional biosafety regulations is required when handling bioactive peptides.

Keywords

 collagen VI peptide, COL6A3 fragment, fibrosis biomarker, ECM-derived peptide, adipose fibrosis, tumor stroma regulator, inflammatory peptide, metabolic dysfunction, collagen-derived signaling peptide, TGF-β activator, ECM remodeling peptide,CAS 1678414-54-4

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