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Updated: Jul 7, 2026
On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
Human stanniocalcin-1 blocks TNF-alpha-induced monolayer permeability in human coronary artery endothelial cells
Changyi Chen1, Md Saha Jamaluddin, Shaoyu Yan
1Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex. 77030, USA. jchen@bcm.tmc.edu
Objective:
Our previous studies revealed upregulation of stanniocalcin-1 (STC1) in cardiac vessels in dilated cardiomyopathy. However, the functional significance of STC1 is unknown. The objective of this study was to determine the effects of STC1 on TNF-alpha-induced monolayer permeability of human coronary artery endothelial cells (HCAECs).
Methods And Results:
Cells were pretreated with STC1 for 30 minutes followed by treatment with TNF-alpha (2 ng/mL) for 24 hours. Monolayer permeability was studied using a transwell system. STC1 pretreatment significantly blocked TNF-alpha-induced monolayer permeability in a concentration- and time-dependent manner. STC1 effectively blocked TNF-alpha-induced downregulation of endothelial tight junction proteins zonula occluden-1 and claudin-1 at both mRNA and protein levels. STC1 also significantly decreased TNF-alpha-induced superoxide anion production. The inhibitory effect of STC1 was specific to TNF-alpha, as it failed to inhibit VEGF-induced endothelial permeability. Furthermore, STC1 partially blocked NF-kappaB and JNK activation in TNF-alpha-treated endothelial cells. JNK inhibitor and antioxidant also effectively blocked TNF-alpha-induced NF-kappaB activation and monolayer permeability in HCAECs.
Conclusions:
STC1 maintains endothelial permeability in TNF-alpha-treated HCAECs through preservation of tight junction protein expression, suppression of superoxide anion production, and inhibition of the activation of NFkappaB and JNK, suggesting an important role for STC1 in regulating endothelial functions during cardiovascular inflammation.
Insights
Stanniocalcin-1 (STC1) protects human coronary artery endothelial cells from TNF-alpha-induced permeability. STC1 preserves tight junctions and reduces inflammation, highlighting its role in cardiovascular health.
Area of Science:
- Cardiovascular Biology
- Endothelial Cell Function
- Molecular Medicine
Background:
- Upregulation of stanniocalcin-1 (STC1) observed in cardiac vessels of dilated cardiomyopathy patients.
- Functional significance of STC1 in endothelial cells remains largely unknown.
Purpose of the Study:
- To investigate the effects of STC1 on tumor necrosis factor-alpha (TNF-alpha)-induced monolayer permeability in human coronary artery endothelial cells (HCAECs).
Main Methods:
- HCAECs were pretreated with STC1, followed by TNF-alpha stimulation.
- Monolayer permeability assessed using a transwell system.
- Expression of tight junction proteins (zonula occluden-1, claudin-1), superoxide anion production, and activation of NF-kappaB and JNK pathways were analyzed.
Main Results:
- STC1 pretreatment significantly inhibited TNF-alpha-induced monolayer permeability in a concentration- and time-dependent manner.
- STC1 preserved tight junction protein expression and reduced superoxide anion production.
- STC1 partially inhibited NF-kappaB and JNK activation, with effects specific to TNF-alpha stimulation.
Conclusions:
- STC1 maintains endothelial barrier integrity in TNF-alpha-treated HCAECs.
- Mechanisms include preserving tight junctions, suppressing oxidative stress, and inhibiting NF-kappaB and JNK signaling.
- STC1 plays a crucial role in regulating endothelial function during cardiovascular inflammation.
