Elucidating the fundamental fibrotic processes driving abdominal adhesion formation

Area of Science:

• Surgical pathology
• Fibroblast biology
• Molecular mechanisms of adhesion formation

Background:

• Abdominal adhesions are fibrotic scars complicating surgery and infection, leading to bowel obstruction, pain, and infertility.
• Limited understanding of adhesion biology hinders development of effective anti-adhesion treatments.

Purpose of the Study:

• To systematically analyze the cellular and molecular origins of abdominal adhesions in mouse and human tissues.
• To identify key molecular pathways and cell types involved in adhesion formation.
• To evaluate potential therapeutic targets for preventing adhesions.

Main Methods:

• Systematic analysis of mouse and human adhesion tissues.
• Single-cell RNA sequencing to identify fibroblast heterogeneity.
• Investigated the role of JUN and PDGFRA in adhesion formation.

Main Results:

• Adhesions primarily originate from the visceral peritoneum.
• Adhesions are formed by polyclonal, proliferating tissue-resident fibroblasts with notable heterogeneity.
• JUN promotes adhesion formation and upregulates PDGFRA; JUN suppression diminishes adhesion formation.

Conclusions:

• JUN is a key promoter of abdominal adhesion formation.
• JUN represents a promising therapeutic target for intra-operative anti-adhesion therapies.
• Targeting JUN could significantly improve outcomes for surgical patients by preventing adhesion-related complications.