MFG-E8 Plays an Important Role in Attenuating Cerulein-Induced Acute Pancreatitis in Mice.
MFG-E8 Plays an Important Role in Attenuating Cerulein-Induced Acute Pancreatitis in Mice.
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作者：
Bu HF;Subramanian S;Geng H;Wang X;Liu F;Chou PM;Du C;De Plaen IG;Tan XD
乳脂球egf因子8 （MFG-E8）是一种分泌糖蛋白，调节组织稳态，具有有效的抗炎特性，并保护组织免受损伤。人胰腺表达MFG-E8；然而，MFG-E8在胰腺中的作用尚不清楚。我们检测了小鼠在基线和cerulein诱导的急性胰腺炎期间胰腺中MFG-E8的表达，并确定MFG-E8是否能减缓胰腺炎的进展，胰腺炎是一种可能危及生命的严重炎症。我们给野生型（WT）和Mfge8敲除（KO）小鼠注射蓝蛋白诱导胰腺炎。免疫印迹分析显示，MFG-E8在小鼠胰腺中组成性表达，在cerulein诱导的急性胰腺炎小鼠中表达增加。原位杂交显示小鼠胰腺导管上皮细胞在基线水平表达Mfge8转录本。在胰腺炎期间，除了导管上皮细胞外，Mfge8转录本在腺泡细胞和内皮细胞中大量表达。在小鼠中敲除Mfge8会加重蛋白诱导的急性胰腺炎的严重程度，并延缓其消退。相比之下，重组MFG-E8可减轻cerulein诱导的急性胰腺炎，促进Mfge8 KO小鼠胰腺损伤的修复。综上所述，我们的研究表明MFG-E8可以保护胰腺免受炎症损伤，促进胰腺组织修复。MFG-E8可能是急性胰腺炎的一个新的治疗靶点。
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 Mfge8 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 Mfge8 transcripts at baseline. During pancreatitis, Mfge8 transcripts were abundantly expressed in acinar cells and endothelial cells in addition to ductal epithelial cells. Knocking out Mfge8 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 Mfge8 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.
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影响因子：
3.7
作者：
Aziz M;Jacob A;Matsuda A;Wu R;Zhou M;Dong W;Yang WL;Wang P
通讯作者：
Wang P
DOI：
10.4049/jimmunol.1200262
发表时间：
2012-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Aziz M;Matsuda A;Yang WL;Jacob A;Wang P
通讯作者：
Wang P
影响因子：
64.5
作者：
Ensslin, MA;Shur, BD
通讯作者：
Shur, BD
影响因子：
29.4
作者：
Lugea, Aurelia;Nan, Li;Pandol, Stephen J.
通讯作者：
Pandol, Stephen J.
影响因子：
5.3
作者：
Hoang, Chinh Q.;Hale, Michael A.;MacDonald, Raymond J.
通讯作者：
MacDonald, Raymond J.