Expression and localization of Muc4/sialomucin complex (SMC) in the adult and developing rat intestine: Implications for Muc4/SMC function

Abstract

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.

The Human Mucin MUC4 Is Transcriptionally Regulated by Caudal-related Homeobox, Hepatocyte Nuclear Factors, Forkhead Box A, and GATA Endodermal Transcription Factors in Epithelial Cancer Cells

“…Clearly the spatio-temporal pattern of expression of Muc4 is organ-and cell-specific. These results are in agreement with previous data in human (12) and rat (48) and confirm the dual role of MUC4, especially in the intestine, as a membrane-associated protein before cytodifferentiation and both as a membraneassociated and secreted protein (localization in secretory granules of goblet cells) after cytodifferentiation. Altogether these studies indicate that MUC4 has a spatio-temporal pattern of expression both in developing human and rodents, which corrobates its important role in cytodifferentiation in both species.…”

A novel bioactive peptide from yoghurts modulates expression of the gel-forming MUC2 mucin as well as population of goblet cells and Paneth cells along the small intestine

“…They are anchored to the apical cell surface of epithelial cells and are a major component of the glycocalyx. In the intestine, MUC4 is one of such prominent transmembrane-associated mucins [31]. In the present study, we showed that proteolysis of caseins by lactic bacteria (L. delbrueckii ssp.…”

The Densely O-Glycosylated MUC2 Mucin Protects the Intestine and Provides Food for the Commensal Bacteria

“…This mucin has its three typical domains next to the large PTS domain at the extracellular cell surface. MUC4 is just as the SEA mucins cleaved during biosynthesis [18]. Most transmembrane mucins are found in the gastrointestinal tract, MUC1, MUC3, MUC4, MUC12, MUC13, MUC16, and MUC17.…”