Division of Pulmonary and Critical Care Medicine
Cedars-Sinai Medical Center

Project title: Syndecan-1 Regulation of Lung Fibrosis

Peter Chen, MD – Cedars-Sinai Medical Center
Cory Hogaboam, PhD – Cedars-Sinai Medical Center

Multidisciplinary Expertise:
Lung Biology, Exosome Biology, Lung Fibrosis

Project Description:
Idiopathic pulmonary fibrosis (IPF) is a fatal progressive lung disease. The overarching concept of IPF pathogenesis is that epithelial damage and dysregulated epithelial repair leads to perturbations of the lung microenvironment that induce various fibrogenic signals to recruit and activate various effector cells causing fibroproliferation. The critical knowledge gap in this paradigm is how epithelial dysfunction produces signals that coordinate effector cells in the pathogenic process. Syndecan-1 is primarily expressed by epithelial cells. Aberrancy of syndecan-1 expression leads to dysregulation of tissue repair. We found that syndecan-1 is overexpressed by the lung epithelium in IPF. We also demonstrated that syndecan-1 is pro-fibrotic in a murine bleomycin-injury model. Moreover, deviations to normal syndecan-1 expression levels promote lung fibrosis by altering miRNAs packaging in exosomes. The current project is to study the mechanisms by which syndecan-1 regulates miRNA loading into exosomes and to determine how syndecan-1 promotes fibrosis through exosomal miRNAs.