Protein Tyrosine Phosphatase- α Amplifies TGF-β-Dependent Pro-Fibrotic Signaling in Lung Fibroblasts.

Protein Tyrosine Phosphatase-α Amplifies TGF-β-Dependent Pro-Fibrotic Signaling in Lung Fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2020 Jun 03;: Authors: Aschner Y, Nelson M, Brenner M, Roybal H, Beke K, Meador C, Foster D, Reynolds PR, Anderson K, Redente EF, Matsuda J, Riches DWH, Groshong SD, Pozzi A, Sap J, Wang Q, Rajshankar D, McCulloch CAG, Zemans RL, Downey GP Abstract Idiopathic Pulmonary Fibrosis (IPF) is a progressive fibrosing lung disease for which treatment remains suboptimal. Fibrogenic cytokines, including transforming growth factor-β, are central to its pathogenesis. Protein Tyrosine Phosphatase-alpha (PTPα) has emerged as a key regulator of fibrogenic signaling in fibroblasts. We have reported that mice globally deficient in PTPα (Ptpra-/-) were protected from experimental pulmonary fibrosis, in part via alterations in TGF-β signaling. The goal of this study was to determine the lung cell types and mechanisms by which PTPα controls fibrogenic pathways and whether these pathways are relevant to human disease. Immunohistochemical analysis of lungs from IPF patients revealed that PTPα was highly expressed by mesenchymal cells in fibroblastic foci and by airway and alveolar epithelial cells. To determine whether PTPα promotes profibrotic signaling pathways in lung fibroblasts and/or epithelial cells, we generated mice with conditional (floxed) Ptpra alleles (Ptpraf/f). These mice were crossed with Dermo1-...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research