Elucidating the fundamental fibrotic processes driving abdominal adhesion formation

Deshka S. Foster, Clement D. Marshall, Gunsagar S. Gulati, Malini S. Chinta, Alan Nguyen, Ankit Salhotra, R. Ellen Jones, Austin Burcham, Tristan Lerbs, Lu Cui, Megan E. King, Ashley L. Titan, R. Chase Ransom, Anoop Manjunath, Michael S. Hu, Charles P. Blackshear, Shamik Mascharak, Alessandra L. Moore, Jeffrey A. Norton, Cindy J. KinAndrew A. Shelton, Michael Januszyk, Geoffrey C. Gurtner, Gerlinde Wernig, Michael T. Longaker

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Adhesions are fibrotic scars that form between abdominal organs following surgery or infection, and may cause bowel obstruction, chronic pain, or infertility. Our understanding of adhesion biology is limited, which explains the paucity of anti-adhesion treatments. Here we present a systematic analysis of mouse and human adhesion tissues. First, we show that adhesions derive primarily from the visceral peritoneum, consistent with our clinical experience that adhesions form primarily following laparotomy rather than laparoscopy. Second, adhesions are formed by poly-clonal proliferating tissue-resident fibroblasts. Third, using single cell RNA-sequencing, we identify heterogeneity among adhesion fibroblasts, which is more pronounced at early timepoints. Fourth, JUN promotes adhesion formation and results in upregulation of PDGFRA expression. With JUN suppression, adhesion formation is diminished. Our findings support JUN as a therapeutic target to prevent adhesions. An anti-JUN therapy that could be applied intra-operatively to prevent adhesion formation could dramatically improve the lives of surgical patients.

Original languageEnglish (US)
Article number4061
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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