Disease relevance of MUC5AC

• In areas of papillary hyperplasia, altered expression of MUC3, MUC5B, and MUC5AC is observed [1].
• Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas [2].
• In addition, on gallbladder tissue sections from subjects with gallstones, increased MUC5AC immunoreactivity was detected in the epithelium and within mucus gel in the lumen [3].
• CONCLUSIONS: Our results suggest that gel forming mucins (more particularly MUC5AC and MUC6) may have a role in epithelial wound healing after mucosal injury in inflammatory bowel diseases in addition to mucosal protection [4].
• There was de novo expression of MUC5AC in 23/36 carcinomas [5].

Psychiatry related information on MUC5AC

• TBM plays a useful role in the differentiation and management of various other disorders, including depression, behavioral disturbances and dementias [6].

High impact information on MUC5AC

• CD34+ human marrow cells not expressing T cell-, B cell-, and myeloid cell-associated antigens (TBM-) were cloned by two-color cell sorting into culture wells containing irradiated marrow stromal cells [7].
• Results in cultured airway epithelial cells showed that samples of asthmatic fluid stimulated mucin (MUC5AC) synthesis severalfold more potently than non-asthmatic fluid [8].
• Both patient antisera containing alpha TBM-Ab were also highly reactive with R3M-1, the 48,000-mol-wt rabbit glycoprotein antigen of experimental alpha TBM disease [9].
• Using a monoclonal anti-tubular basement membrane antibody (alpha TBM-Ab) affinity column, we isolated from collagenase-solubilized human renal tissue (HSRTA) a predominantly 48,000-mol-wt moiety (H3M-1) which is selectively recognized by antisera from two patients with alpha TBM-Ab-associated interstitial nephritis (alpha TBM disease) [9].
• RESULTS: In the 22 RVAs, we found an overexpression of MUC2 and an aberrant expression of MUC5AC [10].

Chemical compound and disease context of MUC5AC

• Two unique nucleotide probes for human tracheobronchial mucin glycoprotein (TBM) were generated via polymerase chain reaction with degenerate primers deduced from the TBM:TR-3A tryptic peptide sequence and were used to isolate a 3.6 kilobase cDNA, clone NP3a, from a human nasal polyp cDNA library [11].
• Novel cytoplasmic proteins of nontypeable Haemophilus influenzae up-regulate human MUC5AC mucin transcription via a positive p38 mitogen-activated protein kinase pathway and a negative phosphoinositide 3-kinase-Akt pathway [12].
• Immunohistochemical study of the expression of MUC6 mucin and co-expression of other secreted mucins (MUC5AC and MUC2) in human gastric carcinomas [13].
• Gefitinib inhibits MUC5AC synthesis in mucin-secreting non-small cell lung cancer cells [14].
• We found that dicumarol, an inhibitor of the NADP(H):quinone oxidoreductase 1 (NQO1), inhibited MUC5AC mRNA expression in A549 lung adenocarcinoma cells and primary normal human bronchial epithelial cells [15].

Biological context of MUC5AC

• However, the mechanisms by which the interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha induce MUC5AC gene expression in normal nasal epithelial cells, and the signal molecules involved, especially in the downstream signaling of mitogen-activated protein (MAP) kinases, remain unclear [16].
• Both cases of MUC6 positivity and 1/5 cases of MUC5AC positivity were confined to the ulcer associated cell lineage [17].
• Intense expression of the MUC5AC gene, suggesting a gastric surface cell phenotype, was demonstrated in 18/21 tumours (86%) [18].
• Analysis of cells isolated by microdissection showed stepwise upregulation of MUC1 and MUC5AC in the development of high-grade PanIN to IDC [19].
• In this study, the organization of MUC5AC has been entirely elucidated showing extensive similarity to the other chromosome 11p15 MUC genes, particularly MUC5B, and providing additional arguments for common evolution from a single ancestral gene [20].

Anatomical context of MUC5AC

• Dual oxidase 1-dependent MUC5AC mucin expression in cultured human airway epithelial cells [21].
• MUC5AC is generally recognized to be a major airway mucin because MUC5AC is highly expressed in the goblet cells of human airway epithelium [16].
• There was no significant correlation between MUC1 and MUC5AC expression in cell lines [19].
• Permanent exposure of mucin-secreting HT-29 cells to benzyl-N-acetyl-alpha-D-galactosaminide induces abnormal O-glycosylation of mucins and inhibits constitutive and stimulated MUC5AC secretion [22].
• Expression of MUC5AC was only seen in individual goblet cells in the trachea, while MUC5B was expressed in the surface epithelium of the trachea at 13 wk but was largely restricted to submucosal glands by 23 wk of gestation [23].

Associations of MUC5AC with chemical compounds

• They were located in the -2627/-2097 and -202/-1 regions of MUC2 and MUC5AC promoters, respectively [24].
• MUC5AC, a Gel-Forming Mucin Accumulating in Gallstone Disease, Is Overproduced via an Epidermal Growth Factor Receptor Pathway in the Human Gallbladder [3].
• The arrangement of cysteine residues in this sequence was very similar to that in the C-terminal regions of MUC2, MUC5AC and human von Willebrand factor [25].
• Cys-domains 1-9 are interspersed by four domains (TR1-TR4) composed of various numbers of MUC5AC-type repeats [20].
• In conclusion, benzyl-N-acetyl-alpha-D-galactosaminide induces abnormal O-glycosylation and altered regulation of MUC5AC secretion [22].

Physical interactions of MUC5AC

• The trefoil protein TFF1 is bound to MUC5AC in human gastric mucosa [26].
• By chemical inhibition, site-directed promoter mutagenesis and electrophoretic mobility-shift assay (EMSA), we demonstrated that PMA induced proteins binding to all three Sp1 sites and that they were all required for full induction of MUC5AC promoter activity [27].

Regulatory relationships of MUC5AC

• Taken together, these studies give additional insights into the molecular mechanism of IL-1beta- and TNF-alpha-induced MUC5AC gene expression and enhance our understanding on mucin hypersecretion during inflammation [16].
• Human neutrophil elastase (HNE) exists in high concentrations (1-20 microM) in airway secretions of these patients and induces overproduction of MUC5AC mucin, a major component of airway mucus [28].
• CONCLUSION: Selective PDE4 inhibition is effective in decreasing EGF induced MUC5AC expression in human airway epithelial cells [29].
• Our researchers have analyzed the changes of AQP5 expression induced by vector-based short hairpin RNA (shRNA) in the human airway submucosal gland cell line (SPC-A1) and observed its regulation on the expression of MUC5AC gene [30].
• IL-13 suppresses MUC5AC gene expression and mucin secretion in nasal epithelial cells [31].
• Inhibition of either CREB or c-Ets1 inhibited ATP-induced MUC5AC gene expression [32].

Other interactions of MUC5AC

• MUC2, MUC4, and MUC5AC are generally undetectable in all cells of normal pancreas tissue [1].
• Hence, change in the synthesis of MUC2 and the de novo appearance of MUC5AC in colorectal carcinomas may be significant events in the adenoma-carcinoma sequence, with possible implications for tumour prognosis [5].
• A reduced expression of MUC4, MUC5AC, and MUC8 was observed in non-small cell carcinomas, regardless of their histologic subtype [33].
• In contrast, MUC5AC, MUC5B, and MUC7 are expressed at later gestational ages concomitant with epithelial cytodifferentiation [34].
• MUC5AC and TFF2 were expressed at similar high levels in each clinical group [35].

Analytical, diagnostic and therapeutic context of MUC5AC

• Immunohistochemistry showed that MUC1 and MUC5AC were highly expressed in invasive ductal carcinomas (IDC) and moderately expressed in high-grade pancreatic intraepithelial neoplasia (PanIN); no staining was observed in normal ducts [19].
• MUC5AC, expressed in first and early second trimester fetal bowel, was never detected in intestinal xenografts [36].
• MUC1-4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR [37].
• Immunocytochemistry and Western blotting confirmed TNFalpha effects on MUC2 and MUC5AC on the protein levels [38].
• MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting [37].

References