STAT3–CyPA signaling pathway in endothelial cell apoptosis

Abstract

Cyclophilin A (CyPA), which is encoded by PPIA, is a ubiquitously expressed intracellular protein and is secreted in response to inflammatory stimuli. CyPA stimulates proinflammatory and apoptosis signaling pathways in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), promotes VSMC migration and proliferation, EC adhesion molecules expression, and inflammatory cell chemotaxis and apoptosis. Therefore, we sought to study the transcriptional regulation of CyPA, we hypothesized that transcription factor STAT3 regulated CyPA expression and activated vascular ECs in vitro in a CyPA-dependent manner. Using RT-qPCR, immunostaining, luciferase and ChIP assays, we found that STAT3 induced CyPA expression depended on its transcriptional activation by binding to a specific region containing the STAT3-responsive element (SRE) in the CyPA promoter. Moreover, with cell viability and apoptosis assays, we identified STAT3 stimulated CyPA-dependent apoptosis of human umbilical vein ECs in vitro.