扣针蛋白在气道平滑肌种的表达.pdfVIP

Differential Regulation of Extracellular Matrix and Soluble Fibulin-1 Levels by TGF-b1 in Airway Smooth Muscle Cells Ling Chen1,2, Qi Ge2,3, Judith L. Black2,3, Linhong Deng1,4*, Janette K. Burgess2,3, Brian G. G. Oliver2,3 1 Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Shapingba, Chongqing, China, 2 Woolcock Institute of Medical Research, Sydney, New South Wales, Australia, 3 Discipline of Pharmacology, The University of Sydney, Sydney, New South Wales, Australia, 4 Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu, China Abstract Fibulin-1 (FBLN-1) is a secreted glycoprotein that is associated with extracellular matrix (ECM) formation and rebuilding. Abnormal and exaggerated deposition of ECM proteins is a hallmark of many fibrotic diseases, such as chronic obstructive pulmonary disease (COPD) where small airway fibrosis occurs. The aim of this study was to investigate the regulation of FBLN-1 by transforming growth factor beta 1 (TGF-b1) (a pro-fibrotic stimulus) in primary human airway smooth muscle 4 2 (ASM) cells from volunteers with and without COPD. Human ASM cells were seeded at a density of 1 610 cells/cm , and stimulated with or without TGF-b1 (10 ng/ml) for 72 hours before FBLN-1 deposition and soluble FBLN-1 were measured. Fold change in FBLN-1 mRNA was measured at 4, 8, 24, 48, 72 hours. In some experiments, cycloheximide (0.5 mg/ml) was used to assess the regulation of FBLN-1 production. TGF-b1 decreased the amount of soluble FBLN-1 both from COPD and non-COPD ASM cells. In contrast, the deposition of FBLN-1 into the ECM was increased