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This modification is associated with various physiological functions such as serine and threonine phosphorylation and Notch signaling. Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of \u03b1-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. We have previously reported that O-GlcNAc-modified proteins and GlcNAc-bearing polymers could interact with cell surface vimentin and desmin. In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K\/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. In addition, the administration of anti-O-GlcNAc antibody to inhibit the interaction exacerbated liver fibrosis in the mice. Moreover, administration of the GlcNAc-bearing polymers into carbon tetrachloride-treated mice could ameliorate liver fibrosis. Thus, O-GlcNAc-modified proteins leaked from dead cells can interact with myofibroblasts and activated stellate cells and function as fibrosis suppressors. Moreover, we anticipate that GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins will be applied as novel therapeutic tools for fibrosis.<\/jats:p>","DOI":"10.1093\/glycob\/cwac067","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T12:13:37Z","timestamp":1664453617000},"page":"17-37","source":"Crossref","is-referenced-by-count":8,"title":["<i>N<\/i>-acetylglucosamine-bearing polymers mimicking O-GlcNAc-modified proteins elicit anti-fibrotic activities in myofibroblasts and activated stellate cells"],"prefix":"10.1093","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4948-9375","authenticated-orcid":false,"given":"Hirohiko","family":"Ise","sequence":"first","affiliation":[{"name":"Institute for Materials Chemistry and Engineering, Kyushu University , 744 Motooka, Nishi-ku, Fukuoka 819-0395 , 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