The Second Clinical Medical College, Lanzhou University, Lanzhou, China.
Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, China.
DNA Cell Biol. 2024 Mar;43(3):141-151. doi: 10.1089/dna.2023.0240. Epub 2024 Jan 12.
Primary cilia are microtubule-based organelles that mediate various biological processes. Pancreatic cells are typically ciliated; however, the role of primary cilia in acute pancreatitis (AP) is largely unknown. Here, we report that the loss of primary cilia, mediated by SHCBP1 (SHC1 binding protein), exerted a provocative effect on AP. Primary cilia are extensively lost in inflamed pancreatic cells and in mouse tissues with AP . Abrogation of primary cilia aggravated lipopolysaccharide (LPS)-induced inflammation in pancreatic cells. Mechanistically, AP induced the overexpression of SHCBP1 mitotic factor, which is localized to the base of primary cilia. SHCBP1 deficiency relieved LPS- and cerulein-induced pancreatitis by preventing the loss of primary cilia and . Collectively, we reveal that inflammation-induced loss of primary cilia aggravates AP. Furthermore, abrogating SHCBP1 to prevent primary cilia loss is an efficient strategy to combat AP.
原发性纤毛是由微管组成的细胞器，参与多种生物学过程。胰腺细胞通常有纤毛；然而，原发性纤毛在急性胰腺炎（AP）中的作用在很大程度上是未知的。在这里，我们报告由 SHCBP1（SHC1 结合蛋白）介导的原发性纤毛缺失对 AP 具有刺激性作用。在炎症胰腺细胞中和具有 AP 的小鼠组织中广泛丢失原发性纤毛。原发性纤毛缺失加重了脂多糖（LPS）诱导的胰腺细胞炎症。在机制上，AP 诱导 SHCBP1 有丝分裂因子的过表达，该因子定位于原发性纤毛的基部。SHCBP1 缺失通过防止原发性纤毛缺失缓解 LPS 和 Cerulein 诱导的胰腺炎。总之，我们揭示了炎症诱导的原发性纤毛缺失会加重 AP。此外，消除 SHCBP1 以防止原发性纤毛缺失是对抗 AP 的有效策略。
