Epithelial-Mesenchymal Transition (EMT) in Active Fibroblastic Foci in IPF/UIP
Osamu Matsubara, Kosuke Miyai, Yuichi Ishikawa, Yukio Nakatani, Eugene J Mark. National Defense Medical College, Tokorozawa, Saitama, Japan; Cancer Institute, Koto-ku, Tokyo, Japan; Chiba University, Chiba, Japan; Massachusetts General Hospital and Harvard Medical School, Boston, MA
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with bad prognosis characterized by interstitial fibrosis with irreversible distortion of pulmonary architecture. The histopathology of IPF includes myofibroblasts within active fibroblastic foci (AFF). Previous studies suggest that lung myofibroblasts are derived from epithelial cells through epithelial-mesenchymal transition (EMT). EMT participates in repair and scar formation following epithelial injury in vitro. AFF are distinct findings and a marker of IPF/usual interstitial pneumonia (UIP). They would seem to be sites where fibrotic responses are initiated. We examined the cellular and molecular mechanisms of EMT responsible for the formation of AFF and their role in tissue remodeling.
Design: We investigated the molecular profile of AFF in 16 video-assisted thoracoscopic surgery (VATS) lung biopsies of IPF/UIP and a variety of control lung samples, focusing on the immunohistochemical expression of the molecules involved in EMT and cellular proliferation, namely E-cadherin, beta-catenin, vimentin, alpha-smooth muscle actin, tissue growth factor (TGF)-beta, connective tissue growth factor, and Ki-67. We used a standard indirect avidin-biotin horseradish peroxidase method with various antigen retrievals.
Results: In IPF/UIP these molecules are abnormally expressed in hyperplastic alveolar cells and mesenchymal cells localised to AFF. The spindle cells expressed alpha-smooth muscle actin and vimentin. The hyperplastic alveolar cells lost in part or in entirety epithelial markers (E-cadherin and beta-catenin) and expressed TGF-beta and connective tissue growth factor. Alveolar cells in controls expressed E-cadherin and beta-catenin. Ki-67 positive alveolar cells and spindle cells were increased compared to the controls.
Conclusions: EMT with abnormal proliferation of cells and re-epithelialisation is at the leading edge of AFF formation. Abnormal proliferation of myofibroblasts also has a role in the remodeling process. TGF-beta presumably stimulates myofibroblast proliferation within AFF.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 286, Tuesday Afternoon