Epithelial MUC1 promotes cell migration, reduces apoptosis and affects levels of mucosal modulators during acetylsalicylic acid (aspirin)-induced gastropathy.
MUC1 is a transmembrane mucin highly expressed in the stomach. Although extensive research has uncovered many of its roles in cancer, knowledge about the functions of MUC1 in normal tissues is limited. In the present study, we showed that acetylsalicylic acid (ASA; aspirin) up-regulated MUC1/Muc1 expression in the gastric mucosa of humans and wild-type (WT) mice. ASA induced mucosal injury in all mice to a similar extent; however, WT animals and those chimaeras with Muc1 on the epithelia recovered faster than Muc1-knockout (KO) mice and chimaeras carrying Muc1 on haemopoietic but not epithelial cells. MUC1 enhanced proliferation and migration of the human gastric cell line MKN-7 and increased resistance to apoptosis. The repeated treatment regime used caused a reduction in cyclo-oxygenase-1 (Cox-1) expression, though WT animals returned faster towards pre-treatment levels and had increased Cox-2 and vascular endothelial growth factor levels during recovery. Thus we found that epithelial Muc1 is more important for the healing process than haemopoietic Muc1 and Muc1/MUC1 facilitates wound healing by enhancing cell migration and proliferation, protecting against apoptosis and mediating expression of mucosal modulators. Thus MUC1 plays essential roles during wound healing and development of treatment modalities targeting enhanced expression of MUC1 may be beneficial to treat mucosal wounds.
*Department of Biomedical Chemistry and Cell Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Debashish
D
Banerjee
*Department of Biomedical Chemistry and Cell Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Harvey Robert
HR
Fernandez
†Laboratory for Transplantation and Regenerative Medicine, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Pradeep Bhatu
PB
Patil
*Department of Biomedical Chemistry and Cell Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Pushpa
P
Premaratne
§Department of Microbiology and Immunology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Marianne
M
Quiding-Järbrink
*Department of Biomedical Chemistry and Cell Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Sara Katarina
SK
Lindén
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001241:Aspirin / Q000633:toxicity*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018396:Mucin-1 / Q000096:biosynthesis*
D018396:Mucin-1; C577056:muc1 protein, mouse; D001241:Aspirin