Biology subjects

Matellan, C.

Publications and source records attributed to Matellan, C..

3 recordsLinked to original sources

bioRxiv2025

TWEAK is increased in ulcerative colitis and contributes to fibroblast-mediated monocyte activation via heterologous non-canonical NF-kB/STAT3 signalling

Background and AimsInteractions between fibroblasts and monocytes have emerged as a contributing factor in IBD pathogenesis and therapy resistance, owing to the ability of both cell types to participate in tissue inflammation and repair. We have previously shown that the TNF superfamily factor TWEAK (TNFSF12) can induce a UC-like inflammatory profile in colonic fibroblasts in vitro, in turn promoting monocyte adhesion and activation. However, the mechanisms underlying fibroblast-monocyte communication and its dysregulation in colitis are incompletely understood. MethodsHere we use co-culture models, human biopsies from ulcerative colitis (UC) patients and healthy donors, and public single-cell transcriptomics to characterise the mechanisms underlying fibroblast-mediated monocyte activation. ResultsWe show that TWEAK-treated inflammatory fibroblasts induce a transcriptional programme that resembles early monocyte/macrophage intermediates in UC and is enriched for genes associated with resistance to anti-TNF (TREM1, OSM, IL1B) and susceptibility to IBD (NOD2, ATG16L1). We find that conditioned media from TWEAK-treated fibroblast causes a sustained activation of STAT3 phosphorylation in monocytes, and that inhibition of the NF-{kappa}B Inducing Kinase (NIK) impairs the ability of inflammatory fibroblasts to activate STAT3 phosphorylation in monocytes, resulting in reduced expression of inflammatory mediators. Using tissues from UC patients, we show that the expansion of CD90+/PDPN+ inflammatory fibroblasts in UC correlates with the accumulation of TWEAK+ myeloid cells in the colonic mucosa, and that these fibroblasts co-localise with infiltrating monocytes in sites of active inflammation. ConclusionTogether, our findings suggest that the TWEAK/NF-{kappa}B/STAT3 axis represents an attractive target to tune inflammatory stroma/monocyte crosstalk.

immunology↗

bioRxiv2022

Retinoid acid receptor β mechanically regulates the activity of pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, characterised by stromal remodelling, elevated matrix stiffness and high metastatic rate. Retinoids, compounds derived from vitamin A, have a history of clinical use in cancer for their anti-proliferative and differentiation effects, and more recently have been explored as anti-stromal therapies in PDAC for their ability to induce mechanical quiescence in cancer associated fibroblasts. Here we demonstrate that retinoic acid receptor {beta} (RAR-{beta}) transcriptionally represses myosin light chain 2 (MLC-2) expression, a key regulatory component of the contractile actomyosin machinery. In turn, MLC-2 downregulation results in decreased cytoskeletal stiffness and traction force generation, impaired response to mechanical stimuli via mechanosensing and reduced ability to invade through the basement membrane.

bioengineering↗

bioRxiv2022

Mesenchymal Stem Cells Sense the Toughness of Nanomaterials and Interfaces

Stem cells are known to sense and respond to a broad range of physical stimuli arising from their extra-cellular environment. In particular, the role of the mechanical properties (Youngs or shear modulus, viscoelasticity) of biomaterials has extensively been shown to have a significant impact on the adhesion, spreading, expansion and differentiation of stem cells. In turn, cells exert forces on their environment that can lead to striking changes in shape, size and contraction of associated tissues, and may result in mechanical disruption and functional failure. However, no study has so far correlated stem cell phenotype and biomaterials toughness. Indeed, disentangling toughness-mediated cell response from other mechanosensing processes has remained elusive as it is particularly challenging to uncouple Youngs or shear moduli from toughness, within a range relevant to cell-generated forces. In this report, we show how the design of macromolecular architecture of polymer nanosheets regulates interfacial toughness, independently to interfacial shear storage modulus, and how this, in turn, controls the expansion of mesenchymal stem cells at liquid interfaces.

bioengineering↗