Overexpression of Sulf2 in idiopathic pulmonary fibrosis

TitleOverexpression of Sulf2 in idiopathic pulmonary fibrosis
Publication TypeJournal Article
Year of Publication2013
AuthorsYue X, Lu J, Auduong L, Sides MD, Lasky JA
JournalGlycobiology
Volume23
Issue6
Pagination709-19
Date Published2013 Jun
ISSN1460-2423
KeywordsAged, Animals, Antibiotics, Antineoplastic, Bleomycin, Cell Line, Tumor, Enzyme Induction, Female, Gene Expression, Heparitin Sulfate, Humans, Idiopathic Pulmonary Fibrosis, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Pneumocytes, Primary Cell Culture, Signal Transduction, Smad Proteins, Sulfotransferases, Transforming Growth Factor beta1
Abstract

Previously, we have shown that heparan sulfate (HS) 6-O-endosulfatase 1 (Sulf1) is a transforming growth factor-β1 (TGF-β1)-responsive gene in normal human lung fibroblasts and functions as a negative feedback regulator of TGF-β1 and that TGF-β1 induces the expression of Sulf1 as well as that of the closely related Sulf2 in a murine model of pulmonary fibrosis. In this study, we focused on the role of Sulf2 in modulating TGF-β1 function and the development of pulmonary fibrosis. We found that Sulf2 mRNA was overexpressed in lung samples from human patients with idiopathic pulmonary fibrosis (IPF), and Sulf2 protein was specifically localized to the hyperplastic type II alveolar epithelial cells (AECs). In vitro, TGF-β1 induced the expression of Sulf2 with accompanied HS 6-O-desulfation in A549 cells, adenocarcinoma cells derived from the type II alveolar epithelium. Using small interference RNA to block Sulf2 expression, we observed a biphasic TGF-β1 response with early enhanced Smad activation, but eventually reduced TGF-β1 target gene expression in Sulf2 knockdown A549 cells compared with the control cells. To study the role of Sulf2 in normal type II AECs, we isolated primary type II cells from wild-type and Sulf2 knockout mice. We observed enhanced Smad activation as well as enhanced TGF-β1 target gene expression in Sulf2 knockout type II AECs compared with wild-type type II AECs. In conclusion, Sulf2 is overexpressed in IPF and may play a role in regulating TGF-β1 signaling in type II AECs.

DOI10.1093/glycob/cwt010
Alternate JournalGlycobiology
PubMed ID23418199
PubMed Central IDPMC3641800
Grant List5 P20 RR018766-10 / RR / NCRR NIH HHS / United States
8 P20 GM103514-10 / GM / NIGMS NIH HHS / United States
R01 HL083480 / HL / NHLBI NIH HHS / United States
R03 HL096949 / HL / NHLBI NIH HHS / United States
R03 HL096949 / HL / NHLBI NIH HHS / United States
R21 HL095865 / HL / NHLBI NIH HHS / United States
R21 HL095865 / HL / NHLBI NIH HHS / United States