Journal: Oxidative Medicine and Cellular Longevity
Article Title: Sphingosine 1-Phosphate-Upregulated COX-2/PGE 2 System Contributes to Human Cardiac Fibroblast Apoptosis: Involvement of MMP-9-Dependent Transactivation of EGFR Cascade
doi: 10.1155/2022/7664290
Figure Lengend Snippet: Schematic signaling pathways are involved in S1P-induced COX-2/PGE 2 expression associated with activation of caspase-3 leading to apoptosis in HCFs. S1P could be upregulated mediated through estrogen/estrogen receptor-stimulated sphingosine kinase-1 (SphK1) activity , binding with S1PR1/3 coupled to G q or G i protein results in MMP9-mediated HB-EGF cleavage leading to activation of EGFR/PI3K/Akt/MAPKs (i.e., p42/p44 MAPK, p38 MAPK, and JNK1/2)-dependent AP-1 c-Jun. The COX-2 transcription and PGE 2 generation are dependently regulated by an S1PR1/3-mediated EGFR transactivation to activate AP-1 binding activity. These signaling pathways contribute to the activation of AP-1 required for COX-2 expression and PGE 2 generation in HCFs.
Article Snippet: EGFR (sc-03-G), MMP9 (sc-10737), Akt (sc-1619), caspase-3 (sc-22140), and phospho-c-Jun (sc-822, Ser 63 ) antibodies were from Santa Cruz (Santa Cruz, CA, USA).
Techniques: Protein-Protein interactions, Expressing, Activation Assay, Activity Assay, Binding Assay