Interleukin 17A promotes glycolysis to activate human hepatic stellate cells by mediating the TRAF2/TRAF5/HuR/PFKFB3 axis
Year: 2024
Type: article
Abstract: Introduction Biliary atresia (BA) is an obliterating fibrous inflammatory bile duct disease in infants. Interleukin 17A (IL-17A) is abnormally expressed in patients with BA; however, the mechanism of its expression is unclear. Material and methods Liver tissues from patients with BA and those with anicteric choledochal cysts (non-BA) were collected. The expression of genes and proteins was determined using RT-qPCR and western blot. Cell biological activities, including viability and proliferation, were evaluated by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assay. Glucose uptake and lactate and ATP levels were examined using commercial kits. The extracellular acidification rate (ECAR) level was evaluated by the XF96 Extracellular Flux analyzer. The interactions among TRAF2, TRAF5, and human antigen R (HuR) were validated using co-immunoprecipitation (Co-IP), RNA immunoprecipitation (RIP), and RNA pull-down. Results In BA patients, IL-17A, TRAF2, TRAF5, and PFKFB3 were highly expressed, and IL-17A expression was positively correlated with PFKFB3, TRAF2, and TRAF5 expression, respectively. IL-17A elevated PFKFB3 expression and promoted glycolysis and the proliferation and fibrosis of hepatic stellate cells (HSCs), which were abolished by 2-deoxy-D-glucose (2-DG) and PFKFB3/TRAF2/TRAF5 silencing. Mechanistically, IL-17A promoted the interactions among HuR, TRAF2 and TRAF5 to form the TRAF2/TRAF5/HuR complex, thereby enhancing PFKFB3 expression. Conclusions IL-17A facilitates glycolysis and HSC fibrosis by promoting TRAF2/TRAF5/HuR complex formation to regulate PFKFB3 expression.
Authors: Tao Jiang, Shuangjie Li, Lian Tang, Yanfang Tan, Wenxian Ouyang
Institution: Hunan Children's Hospital
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $161
OpenAlex ID: W4404600652