Key result
TNF-α-induced COX-2 and PGE2 upregulation in human cardiac fibroblasts is mediated through a TNFR1-dependent MitoROS/PKCα/p38 MAPK and JNK1/2 cascade activating FoxO1 binding to the COX-2 promoter.
Why the study?
Whether TNF-alpha-induced COX-2/PGE2 upregulation is mediated through a ROS-dependent cascade in human cardiac fibroblasts remained elusive.
Population
Human cardiac fibroblasts (HCFs)
Comparison
TNF-alpha stimulation with vs without pathway inhibitors and siRNAs
Design
In vitro mechanistic laboratory study
Authors
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Suggests targets for cardiac fibroblast inflammation; leaves open translation to clinical heart disease.
TNF-α upregulates COX-2 and PGE2 in human cardiac fibroblasts through a complex signaling cascade involving TNFR1, MitoROS, PKCα, p38 MAPK, JNK1/2, and FoxO1.
Yang et al. (2021) studied this question. TNF-α was evaluated on COX-2 protein and mRNA expression and PGE2 synthesis. TNF-α-induced COX-2 and PGE2 upregulation in human cardiac fibroblasts is mediated through a TNFR1-dependent MitoROS/PKCα/p38 MAPK and JNK1/2 cascade activating FoxO1 binding to the COX-2 promoter.
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