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Post-surgical adhesions are triggered by calcium-dependent membrane bridges between mesothelial surfaces.

Nat. Commun. 11:3068 (2020)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Surgical adhesions are bands of scar tissues that abnormally conjoin organ surfaces. Adhesions are a major cause of post-operative and dialysis-related complications, yet their patho-mechanism remains elusive, and prevention agents in clinical trials have thus far failed to achieve efficacy. Here, we uncover the adhesion initiation mechanism by coating beads with human mesothelial cells that normally line organ surfaces, and viewing them under adhesion stimuli. We document expansive membrane protrusions from mesothelia that tether beads with massive accompanying adherence forces. Membrane protrusions precede matrix deposition, and can transmit adhesion stimuli to healthy surfaces. We identify cytoskeletal effectors and calcium signaling as molecular triggers that initiate surgical adhesions. A single, localized dose targeting these early germinal events completely prevented adhesions in a preclinical mouse model, and in human assays. Our findings classifies the adhesion pathology as originating from mesothelial membrane bridges and offer a radically new therapeutic approach to treat adhesions. Surgical adhesions are organ-joining bands of scar tissue that remain clinically untreatable. Here, the authors show that adhesions are formed through expansive mesothelial membrane bridges, and that blocking these with small molecules prevents formation of adhesions in mice.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hospital Readmissions; Smooth-muscle; United-states; Bepridil; Prevention; Obstruction; Morbidity; Surgery; Organs; Cells
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 11, Heft: 1, Seiten: , Artikelnummer: 3068 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus