Acute pancreatitis (AP) is an acute inflammatory abdominal disease frequently associated with intestinal barrier dysfunction. The steroid hormone 17β-estradiol is an estrogen that exhibits anti-inflammatory effects in various inflammatory diseases. However, its potential beneficial effects on AP and the underlying mechanism have not been investigated. 57 patients with AP and 30 healthy volunteers were enrolled in this study. Caerulein-induced human pancreatic duct epithelial (HPDE) cells were used to establish an in vitro research model. Phosphoglycerate mutase 1 (PGAM1) and Signal transducer and activator of transcription 3 (STAT3) were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels were analyzed using ELISA kits and RT-qPCR assay. Reactive oxygen species (ROS), malondialdehyde (MDA), Superoxide dismutase (SOD), and Catalase (CAT) products were detected using special assay kits. Following JASPAR prediction, the binding between STAT3 and the PGAM1 promoter was verified using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. The effects of 17β-estradiol, STAT3, and PGAM1 on Caerulein-induced HPDE cell damage were assessed. The impacts of 17β-estradiol and STAT3 on pancreatic injury in Caerulein-induced AP mouse model. PGAM1 and STAT3 were highly expressed in AP patients and Caerulein-treated HPDE cells. PGAM1 silencing alleviated Caerulein-triggered HPDE cell inflammatory injury and oxidative stress. Mechanistically, STAT3 was a transcription factor of PGAM1 that promoted PGAM1 transcription by directly binding to its promoter region. 17β-estradiol repressed Caerulein-caused HPDE cell inflammatory injury and oxidative stress by regulating the STAT3/PGAM1. In addition, 17β-estradiol treatment attenuated pancreatic injury in cerulein-induced AP mice by regulating STAT3. 17β-estradiol treatment blocked Caerulein-induced HPDE cell inflammatory injury and oxidative stress by targeting the STAT3/PGAM1 axis, providing a promising strategy to protect against AP. • PGAM1 and STAT3 expression were increased in acute pancreatitis patients and Caerulein-induced HPDE cells. • PGAM1 knockdown restrained Caerulein-induced HPDE cell inflammatory damage and oxidative stress. • Transcription factor STAT3 directly induced PGAM1 transcription. • 17β-estradiol and its receptors could inhibit Caerulein-induced HPDE cell injury by regulating the STAT3/ PGAM1 axis.
Shan et al. (Wed,) studied this question.