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Membrane-bound mucins and mucin terminal glycans expression in idiopathic or Helicobacter pylori, NSAID associated peptic ulcers
Yaron Niv, Doron Boltin, Marisa Halpern, Miriam Cohen, Zohar Levi, Alex Vilkin, Sara Morgenstern, Vahig Manugian, Erica St Lawrence, Pascal Gagneux, Sukhwinder Kaur, Poonam Sharma, Surinder K Batra, Samuel B Ho
Yaron Niv, Doron Boltin, Zohar Levi, Alex Vilkin, Department of Gastroenterology, Rabin Medical Center, Tel Aviv University, Beilinson Hospital, Tel Aviv 49100, Israel
Marisa Halpern, Department of Pathology, Rabin Medical Center, Hasharon Hospital, Tel Aviv 49100, Israel
Miriam Cohen, Pascal Gagneux, Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California San Diego, San Diego, CA 92093, United States
Sara Morgenstern, Department of Pathology, Rabin Medical Center, Beilinson Hospital, Tel Aviv 49100, Israel
Vahig Manugian, Erica St Lawrence, Samuel B Ho, Department of Medicine, VA San Diego Healthcare System and University of California San Diego, San Diego, CA 92161, United States
Sukhwinder Kaur, Surinder K Batra, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, United States
Poonam Sharma, Department of Pathology, Creighton University Medical Center, Omaha, NE 68114, United States
Author contributions: Niv Y contributed to acquisition of data, analysis and interpretation of data, statistical analysis, obtained funding, administrative, technical, and material support, study supervision; Boltin D and Halpern M contributed to acquisition of patient data, analysis and interpretation of data; Levi Z and Vilkin A contributed to statistical analysis; Morgenstern S contributed to pathological analyses; Cohen M and Gagneux P contributed to lectin binding experiments and analysis; Manugian V, St Lawrence E, Kaur S, Sharma P and Batra SK contributed to immunohistochemical experiments and analysis; Ho SB contributed to analysis and interpretation of data, statistical analysis, obtained funding, administrative, technical, and material support, study supervision; all authors contributed to final manuscript writing and editing and gave final approval.
Supported by National Institute of Neurological Disorders and Stroke No. P30 NS047101; Neurosciences Microscopy Shared Facility, UCSD from the G Harold and Leila Y Mathers Charitable Foundation No. CSD018; and NIH center grant No. DK080506
Correspondence to: Samuel B Ho, MD, Chief, Department of Medicine, VA San Diego Healthcare System and University of California San Diego, 3350 La Jolla Village Drive, San Diego, CA 92161, United States.
samuel.ho2@va.gov
Telephone: +1-858-6423280 Fax: +1-858-5524327
Received: August 12, 2013
Revised: September 28, 2013
Accepted: November 28, 2013
Published online: October 28, 2014
Processing time: 443 Days and 6.1 Hours
AIM: To determine the expression of membrane-bound mucins and glycan side chain sialic acids in Helicobacter pylori (H. pylori)-associated, non-steroidal inflammatory drug (NSAID)-associated and idiopathic-gastric ulcers.
METHODS: We studied a cohort of randomly selected patients with H. pylori (group 1, n = 30), NSAID (group 2, n = 18), combined H. pylori and NSAID associated gastric ulcers (group 3, n = 24), and patients with idiopathic gastric ulcers (group 4, n = 20). Immunohistochemistry for MUC1, MUC4, MUC17, and staining for Erythrina cristagalli agglutinin and Sambucus nigra agglutinin (SNA) lectins was performed on sections from the ulcer margins.
RESULTS: Staining intensity of MUC17 was higher in H. pylori ulcers (group 1) than in idiopathic ulcers (group 4), 11.05 ± 3.67 vs 6.93 ± 4.00 for foveola cells, and 10.29 ± 4.67 vs 8.00 ± 3.48 for gland cells, respectively (P < 0.0001). In contrast, MUC1 expression was higher in group 4 compared group 1, 9.89 ± 4.17 vs 2.93 ± 5.13 in foveola cells and 7.63 ± 4.60 vs 2.57± 4.50 for glands, respectively (P < 0.0001). SNA lectin staining was increased in group 4, in parallel to elevated MUC1 expression, indicating more abundant α2-6 sialylation in that group.
CONCLUSION: Cytoplasmic MUC17 staining was significantly decreased in the cases with idiopathic ulcer. The opposite was observed for both MUC1 and SNA lectin. This observation may reflect important pathogenic mechanisms, since different mucins with altered sialylation patterns may differ in their protection efficiency against acid and pepsin.
Core tip: Peptic ulcers are diverse in origin, and the proportion of idiopathic gastric ulcers not related to Helicobacter pylori infection or non-steroidal inflammatory drug therapy is increasing. Membrane-bound mucin proteins in peptic ulcer has not been described previously, and are important for understanding of ulcer pathogenesis and subsequently treatment. Major findings of this paper include the observation that MUC17 staining was significantly decreased in idiopathic ulcer cases, whereas MUC1 mucin expression was increased. Idiopathic ulcers also demonstrated higher sialic acid mucin residue staining. These alterations in mucin core proteins and sialylation patterns may be associated with differences in epithelial cytoprotection, and therefore may play a role in ulcer pathogenesis.
