Researchers may have uncovered the cellular pathways behind systemic sclerosis, according to a study published by Ma et al in Nature Communications. Although previous research has found that the overproduction and accumulation of extracellular matrix leads to fibrosis of the skin, cellular participants are still little understood. Researchers used differentiation trajectories at a single-cell level to characterize the main cellular drivers of fibrosis in the skin—with the goal of identifying potential therapeutic targets to better treat patients with systemic sclerosis. The researchers discovered that myofibroblasts and endothelial-to-mesenchymal transitioning cells may function as central communication hubs driving profibrotic signaling pathways in systemic sclerosis, and may therefore be responsible for extracellular matrix deposition. Further, Hippo pathway effectors were found to play a critical role in the differentiation of myofibroblasts and homeostasis of endothelial-to-mesenchymal transitioning cells. After targeting the pathway with verteporfin, they noted that they were able to reverse the profibrotic phenotype in both myofibroblasts and a subset of endothelial cells. The researchers hypothesized that modulating the Hippo pathway could help reduce the burden of systemic sclerosis.
March 14, 2024