Post-surgical adhesions are triggered by calcium-dependent membrane bridges between mesothelial surfaces
| Autor: | Juliane Wannemacher, Herbert B. Schiller, Axel Walch, Kenji Schorpp, Yuval Rinkevich, Fabian J. Theis, Pushkar Ramesh, Annette Feuchtinger, Philipp-Alexander Neumann, Michaela Aichler, Meshal Ansari, Adrian G. Fischer, Maximilian Strunz, Simon Christ, Tim Koopmans, Kamyar Hadian |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Science General Physics and Astronomy Adhesion (medicine) Tissue Adhesions Matrix (biology) General Biochemistry Genetics and Molecular Biology Epithelium Article Cell Line 03 medical and health sciences Mice 0302 clinical medicine Cytosol Imaging Three-Dimensional Postoperative Complications Single-cell analysis medicine Animals Humans Calcium Signaling RNA Small Interfering lcsh:Science Cell adhesion Cytoskeleton Calcium signaling Principal Component Analysis Multidisciplinary Chemistry Adverse effects Cell Membrane Computational Biology General Chemistry medicine.disease Cell biology Mice Inbred C57BL Disease Models Animal 030104 developmental biology Cell culture 030220 oncology & carcinogenesis lcsh:Q Calcium Female Single-Cell Analysis Mesothelial Cell |
| Zdroj: | Nat. Commun. 11:3068 (2020) Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) Nature Communications |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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