TY - JOUR
T1 - Elucidating the fundamental fibrotic processes driving abdominal adhesion formation
AU - Foster, Deshka S.
AU - Marshall, Clement D.
AU - Gulati, Gunsagar S.
AU - Chinta, Malini S.
AU - Nguyen, Alan
AU - Salhotra, Ankit
AU - Jones, R. Ellen
AU - Burcham, Austin
AU - Lerbs, Tristan
AU - Cui, Lu
AU - King, Megan E.
AU - Titan, Ashley L.
AU - Ransom, R. Chase
AU - Manjunath, Anoop
AU - Hu, Michael S.
AU - Blackshear, Charles P.
AU - Mascharak, Shamik
AU - Moore, Alessandra L.
AU - Norton, Jeffrey A.
AU - Kin, Cindy J.
AU - Shelton, Andrew A.
AU - Januszyk, Michael
AU - Gurtner, Geoffrey C.
AU - Wernig, Gerlinde
AU - Longaker, Michael T.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-17883-1
DO - 10.1038/s41467-020-17883-1
M3 - Article
C2 - 32792541
AN - SCOPUS:85089410882
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4061
ER -