Abstract
Syndecan-1 (SDC-1) is a transmembrane proteoglycan of heparin sulfate that can regulate various cell signal transduction pathways in the airway epithelial cells and fibroblasts. Airway epithelial cells and human bronchial fibroblasts are crucial in airway remodeling. However, the importance of SDC-1 in the remodeling of asthmatic airways has not been confirmed yet. The present study was the first to uncover SDC-1 overexpression in the airways of humans and mice with chronic asthma. This study also validated that an increase in SDC-1 expression was correlated with TGFβ1/Smad3-mediated airway remodeling in vivo and in vitro. A small interfering RNA targeting SDC-1 (SDC-1 siRNA) and homo-SDC-1 in pcDNA3.1 (pc-SDC-1) was designed to assess the effects of SDC-1 on TGFβ1/Smad3-mediated collagen I expression in Beas-2B (airway epithelial cells) and HLF-1 (fibroblasts) cells. Downregulation of the SDC-1 expression by SDC-1 siRNA remarkably attenuated TGFβ1-induced p-Smad3 levels and collagen I expression in Beas-2B and HLF-1 cells. In addition, SDC-1 overexpression with pc-SDC-1 enhanced TGFβ1-induced p-Smad3 level and collagen I expression in Beas-2B and HLF-1 cells. Furthermore, the levels of p-Smad3 and collagen I induced by TGFβ1 were slightly increased after the addition of the recombinant human SDC-1 protein to Beas-2B and HLF-1 cells. These findings in vitro were also confirmed in a mouse model. A short hairpin RNA targeting SDC-1 (SDC-1 shRNA) to interfere with SDC-1 expression considerably reduced the levels of p-Smad3 and remodeling protein (α-SMA, collagen I) in the airways induced by ovalbumin (OVA). Similarly, OVA-induced p-Smad3 and remodeling protein levels in airways increased after mice inhalation with the recombinant mouse SDC-1 protein. These results suggested that SDC-1 of airway epithelial cells and fibroblasts plays a key role in the development of airway remodeling in OVA-induced chronic asthma.
Highlights
Asthma is an inflammatory disease of the airways induced by allergens, gastroesophageal reflux, and genetic factors with complex pathogenesis (1)
Results showed that SDC-1 was overexpressed in the lung airways of the asthmatic subjects, and the degree of overexpression in the tracheal epithelium was considerably higher than that around the trachea (Figures 1A, C)
Results showed that SDC-1 expression slightly decreased in the tracheal epithelium and periductal of OVA-induced acute asthma compared with normal mice (Figures 2B, C)
Summary
Asthma is an inflammatory disease of the airways induced by allergens, gastroesophageal reflux, and genetic factors with complex pathogenesis (1). Epithelial cells in the airways undergo interstitial transformation with disease progression, and fibroblasts are activated and differentiated into myofibroblasts (2). These cells produce numerous extracellular matrix proteins, including type I collagen and asmooth muscle actin (a-SMA) (2). These changes in airway composition transform normal repairable injury responses to pathologic consequences, such as loss of epithelial integrity and excessive matrix deposition in interstitial, which, in turn, accelerate the structural remodeling of the airways (3). Large amounts of TGFb1 are secreted after cell injury and other factors, which participate in the regulation of various transcription factors and the synthesis of protein components of the extracellular matrix, thereby accelerating changes in cellular structures (5). TGFb1/Smad[3] signaling transduction plays a key regulatory role in the progression of liver fibrosis (7), pulmonary fibrosis (8), renal fibrosis (9), airway remodeling (10), cardiac structural remodeling (11), skin scar hyperplasia (12), and other diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
