Macrophages are important mediators of inflammation. Our data show stanniocalcin-1 (STC1) decreases macrophage response to chemoattractants and migration across an endothelial monolayer. STC1 also diminishes superoxide generation in macrophages, by inducing uncoupling protein-2 (UCP2), and inhibits the NF-?B pathway. In cultured endothelial cells, STC1 inhibits cytokine-induced changes in permeability and tight junction protein expression. STC1 transgenic mice, which exhibit elevated serum levels and preferential expression of STC1 in macrophages and endothelium, display less inflammatory macrophages in the glomeruli during anti-glomerular basement membrane (GBM) disease, resulting in kidney protection. Overall hypothesis: STC1 suppresses inflammation through inhibition of macrophage recruitment and function, and cytokine-induced increase in endothelial permeability.
In Specific Aim I, we will determine mechanisms of UCP2 upregulation by STC1 and the role of superoxide in STC1-mediated inhibition of NF-?B in macrophages.
In Specific Aim II, we will determine the effect of STC1 on cytokine-induced changes in expression and assembly of tight junction proteins in cultured primary kidney endothelial cells.
In Specific Aim III, in the context of anti-GBM disease, we will examine endothelial permeability of native kidney vessels, as well as kidney inflammation and function, after kidney endothelium-specific or macrophage-specific overexpression or deletion of STC1.

Public Health Relevance

Our preliminary results show stanniocalcin-1 protein inhibits macrophages, stabilizes blood vessels and decreases kidney inflammation. We plan to study how stanniocalcin-1 inhibits macrophages and how it stabilizes blood vessels during inflammation. This is important because available conventional therapies for inflammation are frequently associated with significant side effects, and our proposed experiments could lead to identification of new medications to treat inflammation.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Flessner, Michael Francis
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Huang, Luping; Belousova, Tatiana; Pan, Jenny Szu-Chin et al. (2014) AKI after conditional and kidney-specific knockdown of stanniocalcin-1. J Am Soc Nephrol 25:2303-15
Lecker, Stewart H; Mitch, William E (2011) Proteolysis by the ubiquitin-proteasome system and kidney disease. J Am Soc Nephrol 22:821-4
Han, H Q; Mitch, William E (2011) Targeting the myostatin signaling pathway to treat muscle wasting diseases. Curr Opin Support Palliat Care 5:334-41
Sheikh-Hamad, David (2010) Mammalian stanniocalcin-1 activates mitochondrial antioxidant pathways: new paradigms for regulation of macrophages and endothelium. Am J Physiol Renal Physiol 298:F248-54
Wang, Yanlin; Huang, Luping; Abdelrahim, Maen et al. (2009) Stanniocalcin-1 suppresses superoxide generation in macrophages through induction of mitochondrial UCP2. J Leukoc Biol 86:981-8