Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblasts.

ABSTRACT: 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 e

SUBMITTER: Vijayakumar G 

PROVIDER: S-EPMC11868938 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature