Loss of cells expressing Fibroblast Activation Protein (FAP) has variable effects in models of TGF- β and chronic bleomycin-induced fibrosis.
Loss of cells expressing Fibroblast Activation Protein (FAP) has variable effects in models of TGF-β and chronic bleomycin-induced fibrosis.
Am J Physiol Lung Cell Mol Physiol. 2019 Jun 12;:
Authors: Kimura T, Monslow J, Klampatsa A, Leibowitz M, Sun J, Liousia M, Woodruff P, Moon E, Todd L, Pure E, Albelda SM
Abstract
Fibroblast activation protein (FAP), a cell surface serine protease, is up-regulated on a subset of activated fibroblasts (often distinct from a-smooth muscle actin-expressing myofibroblasts) associated with matrix remodeling, including fibroblasts in idiopathic pulmonary fibrosis. As FAP+ fibroblasts could be pivotal in either breakdown and/or production of collagen and other matrix components, the goal of this study was to define the role of FAP+ cells in pulmonary fibrosis in two established, but different mouse models of chronic lung fibrosis: repetitive doses of intratracheal bleomycin and a single dose of an adenoviral vector encoding constitutively active TGF-β1 (Ad-TGFβ). To determine their role in fibrotic remodeling, FAP-expressing cells were depleted by injection of T cells expressing a chimeric antigen receptor specific for murine FAP in mice with established fibrosis. The contribution of FAP to the function of FAP-expressing cells was assessed in FAP knock-out mice. Using histological analyses, quantification of soluble collagen content, and flow cytometry, we found that loss of FAP+ cells exacerbated f...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Kimura T, Monslow J, Klampatsa A, Leibowitz M, Sun J, Liousia M, Woodruff P, Moon E, Todd L, Pure E, Albelda SM Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research