Transforming Growth Factor-β Gene Transfer to the Lung Induces Myofibroblast Presence and Pulmonary Fibrosis

Interstitial fibrosis and growth factors.

“…In a murine model of asbestosis (187), TGF-[1 activity was found within myofibroblasts with alpha smooth muscle actin, but in contrast, immunolocalization in a rat silicosis model demonstrated co-localization of TGF-,B1 and type 1 collagen mRNA expression within cells not expressing smooth muscle actin. In vitro, TGF-f1 induces expression of alpha smooth muscle actin in lung fibroblasts (188) and produces a phenotype similar to that of the myofibroblasts encountered in the pathology specimens derived from fibrotic lung (85). Furthermore, administration of neutralizing TGF-f1 antibodies to rat lung progenitor fibroblasts in culture resulted in abolition of TGF-11-induced terminal differentiation to post-mitotic functional fibrocytes.…”

Transient Overexpression of TGF-β1 Induces Epithelial Mesenchymal Transition in the Rodent Peritoneum

“…In fibrotic disorders, the myofibroblast has been identified as one of the major cellular components involved in collagen deposition, and its presence correlates with progression of the disease (12). The origin of the myofibroblast has not been clearly defined, but recent studies in bone marrow chimeric mice confirm the role of mesenchymal transition over recruitment of circulating cell populations as the precursors of interstitial myofibroblasts (13).…”

Latent Transforming Growth Factor-β-Binding Protein-4 Regulates Transforming Growth Factor-β1 Bioavailability for Activation by Fibrogenic Lung Fibroblasts in Response to Bleomycin

“…[1][2][3] TGF-␤ is initially synthesized as an inactive latent molecule (termed the small latent TGF-␤ complex or SLC), which consists of an N-terminal pro-domain, the latency associated peptide (LAP), and a C-terminal mature TGF-␤ domain (active TGF-␤). 4,5 During posttranslational processing, the LAP and mature TGF-␤ domains are cleaved by the endopeptidase furin, but the two peptides remain non-covalently associated.…”