Inhibition of TLR4 signaling in adult human cardiac fibroblasts reduces TGF-β induced fibrotic changes, including contractibility, migration, and expression of cytokines and extracellular matrix genes.
Does inhibition of TLR4 signaling reduce TGF-β induced fibrotic changes in cardiac fibroblasts?
TLR4 is a major immune sensor in cardiac fibroblasts, and its inhibition reduces TGF-β induced fibrotic changes, suggesting a potential therapeutic target for cardiac fibrosis.
Fibrosis is one of the major outcomes following injury in the heart. Immune response in the injury niche modulates fibrosis, yet little is known about how cell-autonomous immune signaling in adult cardiac fibroblasts regulates fibrosis. Using FACS, single-cell sequencing of cardiac fibroblasts from Collagen1-α1GFP mice and human heart failure patients, we demonstrate that TLR4 is the major immune sensor expressed in cardiac fibroblasts. Inhibition of TLR4 signaling reduces TGF-β induced fibrotic changes such as contractibility and migration of adult human cardiac fibroblasts in TGF-β treated fibrotic conditions. TGF-β treated cardiac fibroblastss show enhanced cytokine expression, and inhibition of TLR4 signaling reduces the expression of cytokines, thereby reducing TGF-β targets such as extracellular matrix genes. Thus, our data demonstrate that TLR4 and other signaling molecules downstream of TLR4 are expressed in cardiac fibroblast, and inhibition of TLR4 modulates fibrotic changes in vitro.
Vijayakumar et al. (Sat,) conducted a other in Cardiac fibrosis / Heart failure. Inhibition of TLR4 signaling was evaluated on Fibrotic changes (contractibility, migration, cytokine expression, extracellular matrix genes). Inhibition of TLR4 signaling in adult human cardiac fibroblasts reduces TGF-β induced fibrotic changes, including contractibility, migration, and expression of cytokines and extracellular matrix genes.