JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Add like
Add dislike
Add to saved papers

Integrin α4β1 and TLR4 Cooperate to Induce Fibrotic Gene Expression in Response to Fibronectin's EDA Domain.

Alternative splicing of fibronectin increases expression of the EDA+ isoform of fibronectin (EDA+ Fn), a damage-associated molecular pattern molecule, which promotes fibro-inflammatory disease through the activation of toll-like receptors. Our studies indicate that the fibronectin EDA domain drives two waves of gene expression in human dermal fibroblasts. The first wave, seen at 2 hours, consisted of inflammatory genes, VCAM1, and tumor necrosis factor. The second wave, evaluated at 24 hours, was composed of the fibrosis-associated cytokines IL-10 and IL-13 and extracellular matrix genes fibronectin and osteopontin. Gene expression was coordinately regulated by the α4β1 integrin and the innate immune receptor toll-like receptor 4. Additionally, we found a significant toll-like receptor 4/α4β1-dependent enrichment in the ratio of EDA+ Fn to total fibronectin in response to EDA, consistent with EDA+ Fn initiating further production of EDA+ Fn. Our data also suggest that the EDA/α4β1 integrin interaction primes the cell for an enhanced response to toll-like receptor 4 ligands. Our studies provide evidence that remodeling of the fibronectin matrix in injured or diseased tissue elicits an EDA-dependent fibro-inflammatory response in dermal fibroblasts. The data suggest a paradigm of damage-associated molecular pattern-based signaling whereby damage-associated molecular pattern binding integrins cooperate with innate immune receptors to stimulate inflammation and fibrosis.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app