A Profibrotic Phenotype in Naïve and in Fibrotic Lung Myofibroblasts Is Governed by Modulations in Thy-1 Expression and Activation.

Lung fibrosis is characterized by abnormal accumulation of Thy-deficient fibroblasts in the interstitium of the alveolar space. We have previously shown in bleomycin-treated chimeric Thyl-deficient mice with wild-type lymphocytes that Thyl-deficient fibroblasts accumulate and promote fibrosis and an "inflammation-free" environment. Here, we aimed to identify the critical effects of Thy], or the absence of Thyl, in lung myofibroblast profibrotic functions, particularly proliferation and collagen deposition. Using specific Thyl siRNA in Thyl -positive cells, Thyl knockout cells, Thyl cDNA expression vector in Thyl-deficient cells, and Thyl cross-linking, we evaluated cell proliferation (assessed by cell mass and BrdU uptake), differentiation (using immunofluorescence), and collagen deposition (using Sircol assay). We found that myofibroblast Thyl cross-linking and genetic manipulation modulate cell proliferation and expression of Fgf (fibroblast growth factor) and Angtl (angiotensin) receptors (using qPCR) that are involved in myofibroblast proliferation, differentiation, and collagen deposition. In conclusion, lung myofibroblast downregulation of Thyl expression is critical to increase proliferation, differentiation, and collagen deposition.