Article detail · 2021
GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension.
Journal
The Journal of experimental medicineISSN 0022-1007
The ISSN points to another catalog journal; the name is from the YÖKSİS record.
- Year
- 2021
- Type
- article
Data source split
- YÖKSİS YÖKSİS article record
- YÖKSİS venue The Journal of experimental medicine
- Catalog match (ISSN) Journal of Experimental Medicine
- OpenAlex OpenAlex enrichment (abstract, citations, topics)
Abstract
OpenAlex · English
Portal hypertension is a major contributor to decompensation and death from liver disease, a global health problem. Here, we demonstrate homozygous damaging mutations in GIMAP5, a small organellar GTPase, in four families with unexplained portal hypertension. We show that GIMAP5 is expressed in hepatic endothelial cells and that its loss in both humans and mice results in capillarization of liver sinusoidal endothelial cells (LSECs); this effect is also seen when GIMAP5 is selectively deleted in endothelial cells. Single-cell RNA-sequencing analysis in a GIMAP5-deficient mouse model reveals replacement of LSECs with capillarized endothelial cells, a reduction of macrovascular hepatic endothelial cells, and places GIMAP5 upstream of GATA4, a transcription factor required for LSEC specification. Thus, GIMAP5 is a critical regulator of liver endothelial cell homeostasis and, when absent, produces portal hypertension. These findings provide new insight into the pathogenesis of portal hypertension, a major contributor to morbidity and mortality from liver disease.
Topics
Citations
OpenAlex cited_by_count. Not a WoS or Scopus citation count; those sources have no separate column here.
41 citations
OpenAlex cited_by_count (cache / database)
4 publications in the local catalog that cite this work (OpenAlex reference match; not the full global list).
- GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans 2022
- GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans 2022
- GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway 2024
- GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway 2024