Loss of sinusoidal endothelial identity: RAP1A at the crossroads of capillarisation and liver fibrosis : commentary
Liver fibrosis represents a serious worldwide health issue with a prevalence of around 5% in general populations.1 The most relevant aetiologies of liver fibrosis include metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD) and chronic hepatitis B...
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| Main Authors: | , |
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| Format: | Article (Journal) Editorial |
| Language: | English |
| Published: |
April 15, 2026
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| In: |
Gut
Year: 2026, Pages: 1-3 |
| ISSN: | 1468-3288 |
| DOI: | 10.1136/gutjnl-2026-338383 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/gutjnl-2026-338383 Verlag, lizenzpflichtig, Volltext: https://gut-bmj-com.ezproxy.medma.uni-heidelberg.de/content/early/2026/04/15/gutjnl-2026-338383 
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| Author Notes: | Isabel Fabregat, Christian David Schmid |
| Summary: | Liver fibrosis represents a serious worldwide health issue with a prevalence of around 5% in general populations.1 The most relevant aetiologies of liver fibrosis include metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD) and chronic hepatitis B and C infections. Persisting liver fibrosis can lead to irreversible liver cirrhosis with fatal complications such as ascites, variceal haemorrhage and acute-on-chronic liver failure. - - In liver fibrosis, all hepatic cell types undergo a pathological cell differentiation process, finally leading to stellate cell activation and extensive extracellular matrix synthesis. Attention has long been focused on the essential roles of hepatocytes and macrophages in the initiation and progression of liver fibrotic processes.2 3 However, comparatively little attention has been paid to endothelial cells. Liver sinusoidal endothelial cells (LSECs) are highly specialised cells that line the sinuses of the liver, where they are continuously exposed to the bloodstream and its ever-changing molecular composition. Meanwhile, LSECs are regarded as not only an actor that orchestrates organ homeostasis in communication with other hepatic cells, but also as a contributor to liver pathogenesis. During liver fibrogenesis, LSECs undergo a process called ‘pseudocapillarisation’, which results in the loss of their molecular equipment and morphology.4 - - Notch signalling is one of the most important pathways in LSECs. Under physiological conditions, this finely tuned pathway maintains LSEC differentiation and fenestration. However, in pathological conditions such as liver fibrosis, previous results had indicated that over-activation of endothelial Notch signalling leads to LSEC dedifferentiation and accelerated liver fibrogenesis through attenuation of endothelial … |
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| Item Description: | Gesehen am 07.05.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1468-3288 |
| DOI: | 10.1136/gutjnl-2026-338383 |