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Epithelial Deletion of Sulf2 Alters Alveolar Structure and Gene Expression in the Lung
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A3808 - Epithelial Deletion of Sulf2 Alters Alveolar Structure and Gene Expression in the Lung
Author Block: X. Yue1, X. K. Yang1, J. J. Guidry2; 1Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, United States, 2Proteomics Core Facility, Louisiana State University Health Sciences Center, New Orleans, LA, United States.
RATIONALE: Heparan sulfate (HS) 6-O-endosufatase 2 (Sulf2) is one of the two HS 6-O-endosufatases which selectively remove 6-O sulfate groups from HS intra-chain sites on the cell surface and/or in the extracellular matrix. Changes in HS 6-O-sulfation status modulate the interaction and function of HS-binding proteins including cytokines, chemokines, growth factors and morphogens. We have shown previously that conditional epithelial-specific knockout of Sulf2 (Sulf2 CKO) in murine lungs leads to emphysematous changes with enlarged air spaces at baseline, and enhanced susceptibility to bleomycin-induced injury, inflammation and mortality. In this study, we aim to identify the molecular changes in the lung associated with epithelial deletion of Sulf2. METHODS: A proteomic approach was employed to identify differentially expressed proteins in the lungs from wild-type (WT) and Sulf2 CKO mice. Quantitative real time PCR (qRT-PCR) and Western blotting were then performed to confirm differentially expressed proteins. In addition, lung tissues from mice that have been exposed to nicotine vapor or air (control) were also analyzed. RESULTS: Our proteomics approach identified 68 upregulated and 8 downregulated proteins in the lungs from Sulf2 CKO mice compared to WT littermates. Regulators of immune responses and glutathione metabolism were among the upregulated proteins, and heat shock 70 kDa proteins were among the downregulated proteins. QRT-PCR and Western blotting confirmed the overexpression of glutathione S-transferase mu 5 (Gstm5) at both mRNA and protein levels in Sulf2 CKO mice compared to WT controls. Interestingly, Gstm5 mRNA was also increased in lung tissues from nicotine exposed mice compared to air control mice. CONCLUSION: Results from our proteomics study suggest that Sulf2 may play important roles in immune regulation, glutathione metabolism and stress response in the lung. The upregulation of Gstm5 in Sulf2 CKO mice and in mice exposed to nicotine is intriguing, and future studies are warranted to examine how Sulf2 and nicotine regulate the redox status of the lung.
Author Block: X. Yue1, X. K. Yang1, J. J. Guidry2; 1Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, United States, 2Proteomics Core Facility, Louisiana State University Health Sciences Center, New Orleans, LA, United States.
RATIONALE: Heparan sulfate (HS) 6-O-endosufatase 2 (Sulf2) is one of the two HS 6-O-endosufatases which selectively remove 6-O sulfate groups from HS intra-chain sites on the cell surface and/or in the extracellular matrix. Changes in HS 6-O-sulfation status modulate the interaction and function of HS-binding proteins including cytokines, chemokines, growth factors and morphogens. We have shown previously that conditional epithelial-specific knockout of Sulf2 (Sulf2 CKO) in murine lungs leads to emphysematous changes with enlarged air spaces at baseline, and enhanced susceptibility to bleomycin-induced injury, inflammation and mortality. In this study, we aim to identify the molecular changes in the lung associated with epithelial deletion of Sulf2. METHODS: A proteomic approach was employed to identify differentially expressed proteins in the lungs from wild-type (WT) and Sulf2 CKO mice. Quantitative real time PCR (qRT-PCR) and Western blotting were then performed to confirm differentially expressed proteins. In addition, lung tissues from mice that have been exposed to nicotine vapor or air (control) were also analyzed. RESULTS: Our proteomics approach identified 68 upregulated and 8 downregulated proteins in the lungs from Sulf2 CKO mice compared to WT littermates. Regulators of immune responses and glutathione metabolism were among the upregulated proteins, and heat shock 70 kDa proteins were among the downregulated proteins. QRT-PCR and Western blotting confirmed the overexpression of glutathione S-transferase mu 5 (Gstm5) at both mRNA and protein levels in Sulf2 CKO mice compared to WT controls. Interestingly, Gstm5 mRNA was also increased in lung tissues from nicotine exposed mice compared to air control mice. CONCLUSION: Results from our proteomics study suggest that Sulf2 may play important roles in immune regulation, glutathione metabolism and stress response in the lung. The upregulation of Gstm5 in Sulf2 CKO mice and in mice exposed to nicotine is intriguing, and future studies are warranted to examine how Sulf2 and nicotine regulate the redox status of the lung.
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