Rong Min, Rossi Edmund A, Zhang Jin, McNeer Richard R, van den Brande Jan M H, Yasin Mohammad, Weed Donald T, Carothers Carraway Coralie A, Thompson John F, Carraway Kermit L
Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida 33101, USA.
J Cell Physiol. 2005 Jan;202(1):275-84. doi: 10.1002/jcp.20121.
Muc4/sialomucin complex (SMC) is a high molecular mass heterodimeric membrane mucin, encoded by a single gene, and originally discovered in a highly metastatic ascites rat mammary adenocarcinoma. Subsequent studies have shown that it is a prominent component of many accessible and vulnerable epithelia, including the gastrointestinal tract. Immunoblot and immunofluorescence analyses demonstrated that Muc4/SMC expression in the rat small intestine increases from proximal to distal regions and is located predominantly in cells at the base of the crypts. These cells were postulated to be Paneth cells, based on their location, morphology, and secretory granule content. Immunohistochemistry indicated the presence of Muc4/SMC in these granules. Muc4/SMC expression was higher in the rat colon than small intestine and was abundantly present in colonic goblet cells, but not in goblet cells in the small intestine. Immunohistochemistry also suggested the presence of MUC4 in human colonic goblet cells. Biochemical analyses indicated that rat colonic Muc4/SMC is primarily the soluble form of the membrane mucin. Analyses of Muc4/SMC during development of the rat gastrointestinal tract showed its appearance at embryonic day 14 of the esophagus and at day 15 at the surface of the undifferentiated stratified epithelium at the gastroduodenal junction, then later at cell surfaces in the more distal regions of the differentiated epithelium of the small intestine, culminating in expression as an intracellular form in the crypts of the small intestine at about day 21. Limited expression in the colon was observed during development before birth at cell surfaces, with expression as an intracellular form in the goblet cells arising during the second week after birth. These results suggest that membrane mucin Muc4/SMC serves different functions during development of the intestine in the rat, but is primarily a secreted product in the adult animal.
黏蛋白4/唾液黏蛋白复合物（SMC）是一种高分子量异二聚体膜黏蛋白，由单个基因编码，最初在具有高度转移性的腹水大鼠乳腺腺癌中被发现。随后的研究表明，它是许多易接触和易受损上皮组织的重要组成部分，包括胃肠道。免疫印迹和免疫荧光分析表明，大鼠小肠中Muc4/SMC的表达从近端到远端区域逐渐增加，且主要位于隐窝底部的细胞中。基于这些细胞的位置、形态和分泌颗粒内容物，推测这些细胞为潘氏细胞。免疫组织化学显示这些颗粒中存在Muc4/SMC。Muc4/SMC在大鼠结肠中的表达高于小肠，且大量存在于结肠杯状细胞中，但在小肠杯状细胞中不存在。免疫组织化学还提示人结肠杯状细胞中存在MUC4。生化分析表明，大鼠结肠Muc4/SMC主要是膜黏蛋白的可溶性形式。对大鼠胃肠道发育过程中Muc4/SMC的分析表明，它在胚胎第14天出现在食管，在第15天出现在胃十二指肠交界处未分化复层上皮的表面，随后出现在小肠分化上皮更远端区域的细胞表面，最终在大约第21天以细胞内形式在小肠隐窝中表达。在出生前发育过程中，结肠中在细胞表面观察到有限的表达，出生后第二周在杯状细胞中以细胞内形式表达。这些结果表明，膜黏蛋白Muc4/SMC在大鼠肠道发育过程中发挥不同功能，但在成年动物中主要是一种分泌产物。
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