Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Cancer Lett. 2023 Dec 1;578:216455. doi: 10.1016/j.canlet.2023.216455. Epub 2023 Oct 19.
Ubiquitin-binding associated protein 2 (UBAP2) is reported to promote macropinocytosis and pancreatic adenocarcinoma (PDAC) growth, however, its role in normal pancreatic function remains unknown. We addressed this knowledge gap by generating UBAP2 knockout (U2KO) mice under a pancreas-specific Cre recombinase (Pdx1-Cre). Pancreatic architecture remained intact in U2KO animals, but they demonstrated slight glucose intolerance compared to controls. Upon cerulein challenge to induce pancreatitis, U2KO animals had reduced levels of several pancreatitis-relevant cytokines, amylase and lipase in the serum, reduced tissue damage, and lessened neutrophil infiltration into the pancreatic tissue. Mechanistically, cerulein-challenged U2KO animals revealed reduced NF-κB activation compared to controls. In vitro promoter binding studies confirmed the reduction of NF-κB binding to its target molecules supporting UBAP2 as a new regulator of inflammation in pancreatitis and may be exploited as a therapeutic target in future to inhibit pancreatitis.
泛素结合相关蛋白 2 (UBAP2) 据报道可促进巨胞饮作用和胰腺腺癌 (PDAC) 的生长，但它在正常胰腺功能中的作用尚不清楚。我们通过在胰腺特异性 Cre 重组酶 (Pdx1-Cre) 下生成 UBAP2 敲除 (U2KO) 小鼠来解决这一知识空白。U2KO 动物的胰腺结构保持完整，但与对照组相比，它们表现出轻微的葡萄糖不耐受。在用 Cerulein 诱导胰腺炎时，U2KO 动物的血清中几种与胰腺炎相关的细胞因子、淀粉酶和脂肪酶水平降低，组织损伤减少，胰腺组织中的中性粒细胞浸润减少。在机制上，与对照组相比，Cerulein 刺激的 U2KO 动物的 NF-κB 激活减少。体外启动子结合研究证实 NF-κB 与其靶分子的结合减少，支持 UBAP2 作为胰腺炎炎症的新调节剂，并可能在未来被用作抑制胰腺炎的治疗靶点。
