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<p>Mucin-2 (MUC2) plays a crucial role in maintaining intestinal homeostasis during acute pancreatitis (AP). We aimed to investigate the role of B3GNT7 (β-1,3-N-acetylglucosamine transferase) in the O-glycosylation of MUC2 in AP. We used two mouse models of AP induced by caerulein/lipopolysaccharide or L-arginine, and observed colonic goblet cells using electron microscopy, noting that Golgi damage was linked to decreased levels of mature MUC2. Golgi stress–associated proteins (reduced GM130 and elevated GOLPH3) were identified using immunofluorescence. Transcriptome analysis revealed the downregulation of <i>B3gnt7</i>, a glycosyltransferase that is highly enriched in the Golgi apparatus of goblet cells in AP mice. B3GNT7 expression was negatively correlated with pancreatic and colonic pathological scores. In patients with AP, intestinal B3GNT7 levels are markedly reduced and correlated with Ranson scores, C-reactive protein levels, and intestinal permeability markers (serum diamine oxidase and D-lactate). Adeno-associated virus (AAV)-mediated knockdown of B3GNT7 reduced O-glycosylated MUC2 levels, exacerbated pancreatic and systemic inflammation, and worsened intestinal permeability and dysbiosis. In vitro, LPS-treated HT-29 cells exhibited Golgi stress (decreased levels of B3GNT7 and O-glycosylated MUC2) that was reversed by L-glutathione (GSH). These findings demonstrate that B3GNT7 downregulation, mediated by Golgi stress, disrupts MUC2 O-glycosylation, exacerbating AP by impairing intestinal homeostasis.</p>

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B3GNT7 preserves intestinal barrier integrity: a key defense mechanism against acute pancreatitis progression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月31日

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  • Jia Hu,
  • Yang Fu,
  • Zehua Huang,
  • Nuoming Yin,
  • Binqiang Xu,
  • Huizhen Huang,
  • Mengyan Cui,
  • Qixiang Mei,
  • Chunlan Huang,
  • Yue Zeng,
  • Junjie Fan

摘要

Mucin-2 (MUC2) plays a crucial role in maintaining intestinal homeostasis during acute pancreatitis (AP). We aimed to investigate the role of B3GNT7 (β-1,3-N-acetylglucosamine transferase) in the O-glycosylation of MUC2 in AP. We used two mouse models of AP induced by caerulein/lipopolysaccharide or L-arginine, and observed colonic goblet cells using electron microscopy, noting that Golgi damage was linked to decreased levels of mature MUC2. Golgi stress–associated proteins (reduced GM130 and elevated GOLPH3) were identified using immunofluorescence. Transcriptome analysis revealed the downregulation of B3gnt7, a glycosyltransferase that is highly enriched in the Golgi apparatus of goblet cells in AP mice. B3GNT7 expression was negatively correlated with pancreatic and colonic pathological scores. In patients with AP, intestinal B3GNT7 levels are markedly reduced and correlated with Ranson scores, C-reactive protein levels, and intestinal permeability markers (serum diamine oxidase and D-lactate). Adeno-associated virus (AAV)-mediated knockdown of B3GNT7 reduced O-glycosylated MUC2 levels, exacerbated pancreatic and systemic inflammation, and worsened intestinal permeability and dysbiosis. In vitro, LPS-treated HT-29 cells exhibited Golgi stress (decreased levels of B3GNT7 and O-glycosylated MUC2) that was reversed by L-glutathione (GSH). These findings demonstrate that B3GNT7 downregulation, mediated by Golgi stress, disrupts MUC2 O-glycosylation, exacerbating AP by impairing intestinal homeostasis.