Increased plasma clusterin and miR-21 in acute pancreatitis.

Abstract

Acute pancreatitis is an inflammatory condition associated with a high complication rate and an increased risk of death. The diagnosis can be made by history, physical examination, and the results of diagnostic tests [1]. During an attack of acute pancreatitis, the elevation of alanine aminotransferase (ALT) to >150 IU/L is predictive of a biliary cause [2]. A metaanalysis indicated that this threefold elevation in ALT has a positive predictive value of 95% in diagnosing acute gallstone pancreatitis [3]. Despite the advances in investigational modalities and research techniques, the exact pathogenesis of acute pancreatitis is still unclear. Therefore, identifying the severe form early is one of the major challenges in managing severe acute pancreatitis. MiR-21, a multifunctional miRNA with inflammationrelated roles, regulates different types of inflammatory mediators and involves in the development of experimental acute pancreatitis in mice. In addition, miR-21-3p expression level correlates with the severity of the disease [4], and miR-21 deficiency protects against caeruleinor L-arginine-induced acute pancreatitis in mice. miR-21 is significantly upregulated in type 1 autoimmune pancreatitis compared to healthy adult and chronic pancreatitis. The number of miR-21-5p positive inflammatory cells was significantly elevated in acute pancreatitis [5], suggesting that miR-21-5p may be involved in the regulation of effector pathways in the pathophysiology of acute pancreatitis, thus differentiating acute pancreatitis from chronic pancreatitis. Apolipoprotein J/Clusterin is a predominantly secreted glycoprotein induced in several tissues in response to injury. It is overexpressed in the pancreas at the onset of chronic pancreatitis in vivo and in cultured acinar cells in response to various stimuli in vitro, suggesting that clusterin has a regulatory role in the exocrine pancreas [6]. Clusterin is also overexpressed in pancreatic cancer tissues and cell lines, but not in the normal pancreas. In a murine acute pancreatitis model, clusterin is overexpressed in stressed exocrine pancreas during the acute phase of pancreatitis [7], and increases dramatically with severity [8]. Whether serum clusterin levels could be used for the diagnosis of acute pancreatitis is unclear. We therefore hypothesized that levels of clusterin and miR-21 have value in the diagnosis and management of acute pancreatitis. We tested our hypothesis in 147 patients with acute pancreatitis; 92 males: mean/range 43.6 (18–86) years; 55 females: 41.6 (22–76) years were admitted to the affiliated hospital of Qingdao University within 72 hours after the onset of disease between January 2015 and October 2019. The patients were diagnosed according to the criteria of the revised Atlanta classification [1]. Before admission, all the patients had had abdominal ultrasound to exclude cholecystolithiasis and/or ductal gallstones and splenic and/or portal vein thrombosis. Blood was collected upon admission. Exclusion criteria were pregnancy, age <18 years, malignancy-related acute pancreatitis, history of chronic pancreatitis, hepatic cirrhosis, receiving early intervention or surgery due to abdominal compartment syndrome or other reasons before admission, or severe systemic diseases. Clinical information is required for severity assessment using the Revised Atlanta Classification criteria with mild, moderate, and severe acute pancreatitis [1]. The Ethics committee of the Affiliated Hospital of Qingdao University approved our retrospective single-centre study and an informed written consent was obtained from all subjects before inclusion. Control subjects n = 44) were randomly selected from a general medical outpatient clinic when he/she needed to have a blood sample drawn for other reasons or was willing to provide the blood sample for research purposes. Peripheral blood samples were collected into EDTAvacutainers, were placed upright for 20 to 25 min, and centrifuged at room temperature at 600 g for 30 min, and the supernatant was further centrifuged at 24°C at 1500 g for 10 min. Plasma was aliquoted and stored at