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<p>Postoperative peritoneal adhesion (PA), a prevalent complication of abdominal surgery, arises from aberrant healing of the injured peritoneum. This process involves mesothelial cell trans-differentiation into myofibroblast-like cells, driving peritoneal matrix remodeling and pathological fibrous band formation between organs. Existing therapeutic strategies to prevent PA exhibit limited efficacy, underscoring the need for previously unrecognized mechanistic insights into PA pathogenesis. Here, we elucidate the role of autophagy in mesothelial cell transition and PA development. Utilizing a murine PA model coupled with comprehensive in vitro analyses, we demonstrate that HMGB1-mediated autophagy facilitates TGF-β mediated mesothelial cell trans-differentiation. Specifically, autophagic degradation of E-cadherin counteracts TGF-β-driven mesothelial transition. Pharmacological activation of autophagy via rapamycin or recombinant HMGB1 potentiated this transition, whereas HMGB1 inhibitor (glycyrrhizin) or autophagy suppressor (spautin-1) markedly attenuated it. Crucially, early postoperative administration of glycyrrhizin or spautin-1 significantly reduced PA severity. Our findings unveil autophagy and HMGB1 as pivotal regulator targets of mesothelial plasticity during PA formation, provide mechanistic insights into peritoneum repair, and propose novel therapeutic avenues for PA prevention.</p>

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HMGB1-enhanced autophagic degradation of E-cadherin facilitates mesothelial trans-differentiation and postoperative peritoneal adhesion

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月30日

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  • Xuetao Yuan,
  • Shuting Yang,
  • Chao Qu,
  • Rui Zhang,
  • Yaru Ren,
  • Yanjun Sun,
  • Enmeng Li,
  • Gan Li,
  • Junxiang Zhang,
  • Jiayin Du,
  • Tianli Shen,
  • Zhengdong Jiang,
  • Xuqi Li

摘要

Postoperative peritoneal adhesion (PA), a prevalent complication of abdominal surgery, arises from aberrant healing of the injured peritoneum. This process involves mesothelial cell trans-differentiation into myofibroblast-like cells, driving peritoneal matrix remodeling and pathological fibrous band formation between organs. Existing therapeutic strategies to prevent PA exhibit limited efficacy, underscoring the need for previously unrecognized mechanistic insights into PA pathogenesis. Here, we elucidate the role of autophagy in mesothelial cell transition and PA development. Utilizing a murine PA model coupled with comprehensive in vitro analyses, we demonstrate that HMGB1-mediated autophagy facilitates TGF-β mediated mesothelial cell trans-differentiation. Specifically, autophagic degradation of E-cadherin counteracts TGF-β-driven mesothelial transition. Pharmacological activation of autophagy via rapamycin or recombinant HMGB1 potentiated this transition, whereas HMGB1 inhibitor (glycyrrhizin) or autophagy suppressor (spautin-1) markedly attenuated it. Crucially, early postoperative administration of glycyrrhizin or spautin-1 significantly reduced PA severity. Our findings unveil autophagy and HMGB1 as pivotal regulator targets of mesothelial plasticity during PA formation, provide mechanistic insights into peritoneum repair, and propose novel therapeutic avenues for PA prevention.