Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Center for Intestinal and Liver Inflammation Research, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Cells. 2021 Mar 25;10(4):728. doi: 10.3390/cells10040728.
Milk fat globule-EGF factor 8 (MFG-E8) is a secreted glycoprotein that regulates tissue homeostasis, possesses potent anti-inflammatory properties, and protects against tissue injury. The human pancreas expresses MFG-E8; however, the role of MFG-E8 in the pancreas remains unclear. We examined the expression of MFG-E8 in the pancreas at baseline and during cerulein-induced acute pancreatitis in mice and determined whether MFG-E8 attenuates the progression of pancreatitis, a serious inflammatory condition that can be life-threatening. We administered cerulein to wild-type (WT) and knockout (KO) mice to induce pancreatitis. Immunoblot analysis showed that MFG-E8 is constitutively expressed in the murine pancreas and is increased in mice with cerulein-induced acute pancreatitis. In situ hybridization revealed that ductal epithelial cells in the mouse pancreas express transcripts at baseline. During pancreatitis, transcripts were abundantly expressed in acinar cells and endothelial cells in addition to ductal epithelial cells. Knocking out in mice exacerbated the severity of cerulein-induced acute pancreatitis and delayed its resolution. In contrast, administration of recombinant MFG-E8 attenuated cerulein-induced acute pancreatitis and promoted repair of pancreatic injury in KO mice. Taken together, our study suggests that MFG-E8 protects the pancreas against inflammatory injury and promotes pancreatic tissue repair. MFG-E8 may represent a novel therapeutic target in acute pancreatitis.
牛奶脂肪球表皮生长因子 8（MFG-E8）是一种分泌型糖蛋白，可调节组织内稳态，具有强大的抗炎特性，并可预防组织损伤。人类胰腺表达 MFG-E8；然而，MFG-E8 在胰腺中的作用尚不清楚。我们检测了正常小鼠胰腺和胰腺腺泡细胞蛋白水解酶诱导性急性胰腺炎（cerulein-induced acute pancreatitis，CIA）模型中 MFG-E8 的表达情况，并研究了 MFG-E8 是否可以减轻这种严重的炎症性疾病（可能危及生命）的进展。我们给野生型（WT）和 MFG-E8 基因敲除（KO）小鼠腹腔注射 cerulein 诱导 CIA。免疫印迹分析显示 MFG-E8 在正常小鼠胰腺中持续表达，在 CIA 模型中表达增加。原位杂交显示，正常胰腺导管上皮细胞表达 转录本。在 CIA 中，除了导管上皮细胞外，腺泡细胞和内皮细胞也大量表达 转录本。在 KO 小鼠中敲除 MFG-E8 会加重 CIA 的严重程度并延迟其恢复。相反，给予重组 MFG-E8 可减轻 CIA 并促进 KO 小鼠的胰腺损伤修复。综上，我们的研究表明 MFG-E8 可保护胰腺免受炎症损伤，并促进胰腺组织修复。MFG-E8 可能成为急性胰腺炎的一个新的治疗靶点。
