Makale detayı · 2021
GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension.
Dergi
The Journal of experimental medicineISSN 0022-1007
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- Yıl
- 2021
- Tür
- article
Veri kaynağı ayrımı
- YÖKSİS YÖKSİS makale kaydı
- YÖKSİS dergi adı The Journal of experimental medicine
- Katalog eşleşmesi (ISSN) Journal of Experimental Medicine
- OpenAlex OpenAlex zenginleştirmesi (özet, atıf, konular)
Özet
OpenAlex · İngilizce
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.
Konular
Atıflar
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41 atıf
OpenAlex cited_by_count (önbellek / veritabanı)
Yerel katalogda bu makaleye atıf yapan 4 yayın (OpenAlex referans eşleşmesi; tam dünya listesi değildir).
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