Tenascin-C Dynamics in Extracellular Matrix Biology

Tenascin-C (TNC) is a prominent matricellular glycoprotein of the extracellular matrix that orchestrates a diverse array of cellular processes through dynamic spatiotemporal expression and modular interactions. Comprising an oligomeric hexameric core and multiple functional domains, TNC modulates cell adhesion, migration and signalling by engaging receptors such as integrins and toll-like receptor 4, and by binding growth factors and glycosaminoglycans. Its expression is low in most healthy adult tissues but is rapidly upregulated during embryogenesis, wound repair, inflammation, fibrosis and tumour stroma remodelling. Alternative splicing of fibronectin type III-like repeats generates numerous isoforms with distinct adhesive and signalling properties, while post-translational modifications further diversify its proteoforms. Through mechanotransduction, TNC contributes to tissue elasticity and resilience under mechanical stress, and it influences immune cell recruitment and activation by modulating chemokine gradients. In pathophysiological contexts, aberrant TNC deposition is implicated in chronic inflammation, atherosclerosis, tumour growth and metastasis, making it both a biomarker and a therapeutic target. Innovative drug-delivery strategies exploit TNC domains for selective targeting of diseased sites, and refined assays for total versus isoform-specific TNC are enhancing diagnostic precision. The global significance of TNC dynamics lies in its central role as a regulator of matrix biology, with practical applications spanning regenerative medicine, cancer therapy and immunomodulation.

Research from Nature Portfolio

A seminal mapping of sites within TNC that directly interact with toll-like receptor 4 has elucidated how specific epitopes serve as endogenous triggers of sterile inflammation. By identifying cooperative binding regions, this work defined a molecular code that designates matrix proteins for innate immune surveillance during tissue damage and tumour progression. The findings advance our understanding of TNC as a damage-associated molecular pattern and suggest avenues for therapeutic modulation of sterile inflammatory pathways.

Tenascin-C Dynamics in Extracellular Matrix Biology publication trend

The graph below shows the total number of articles in tenascin-c dynamics in extracellular matrix biology across all publications each year (not limited to Nature Index journals).

Technical terms

Tenascin-C: A large, multimodular glycoprotein of the extracellular matrix that influences cell adhesion, migration and signalling.

Extracellular matrix (ECM): A complex network of proteins and polysaccharides surrounding cells, providing structural support and regulating biochemical signals.

Matricellular protein: A non-structural ECM component that modulates cell function by interacting with cell surface receptors and other matrix molecules.

Isoform: A variant of a protein arising from alternative splicing or post-translational modification, often with distinct functional properties.

Alternative splicing: A process by which different combinations of exons are joined to produce multiple mRNA transcripts from a single gene.

References

1. The role of TNC in atherosclerosis and drug development opportunities. International Journal of Biological Sciences (2024).
2. Extracellular matrix complexity in biomarker studies: a novel assay detecting total serum tenascin-C reveals different distribution to isoform-specific assays. Frontiers in Immunology (2023).
3. Chemokine Binding to Tenascin-C Influences Chemokine-Induced Immune Cell Migration. International Journal of Molecular Sciences (2023).
4. Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers. Nature Communications (2017).
5. Tenascin C Promiscuously Binds Growth Factors via Its Fifth Fibronectin Type III-Like Domain. PLOS ONE (2013).
6. Tenascin-C and mechanotransduction in the development and diseases of cardiovascular system. Frontiers in Physiology (2014).