SENP1 attenuates hypoxiareoxygenation injury in liver sinusoid endothelial cells by relying on the HIF1α signaling pathway.
Mol Med Rep
; 29(4)2024 04.
Article
en En
| MEDLINE
| ID: mdl-38426545
ABSTRACT
Liver sinusoidal endothelial cells (LSECs) have an important role in hepatic ischemiareperfusion injury (I/R), but the specific molecular mechanism of action is unknown. LSEC proliferation is regulated and fenestration is maintained via the Sentrin/SUMOspecific protease 1 (SENP1)/hypoxiainducible factor1α (HIF1α) signaling axis under hypoxic conditions. In the present study, a hypoxiareoxygenation (HR) injury model was established using mouse LSECs to explore the relationship between SENP1 and HR injury in vitro, and the specific underlying mechanism was identified, revealing new targets for the clinical attenuation of hepatic I/R injury. Following the culture of LSECs under HR conditions, it was demonstrated that the expression of SENP1 was upregulated by reverse transcriptionquantitative polymerase chain reaction and western blotting (WB). In addition, scanning electron microscopy indicated that fenestrae damage was increased, a Cell Counting Kit8 assay demonstrated that the proliferation of cells was impaired and flow cytometry showed that apoptosis was increased. After silencing SENP1 expression with short interfering RNA, the proliferation activity of LSECs decreased, the fenestrae damage increased, the apoptosis rate increased and the expression levels of SENP1, HIF1α, heme oxygenase and Bcl2 were downregulated (as demonstrated by WB), while the expression levels of apoptosisrelated proteins, cleavedcaspase3 and Bax, were upregulated. Enzymelinked immunosorbent assay detection showed that the level of vascular endothelial growth factor in the supernatant decreased and the level of IL6 and TNFα increased. Following the administration of an HIF1α signaling pathway agonist, the situation was reversed. These results therefore suggested that SENP1 attenuated the reduction in proliferation, apoptosis and fenestration of LSECs observed following HR injury through the HIF1α signaling pathway. In conclusion, SENP1 may attenuate HR injury in LSECs in a HIF1α signaling pathwaydependent manner.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptido Hidrolasas
/
Células Endoteliales
Límite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Año:
2024
Tipo del documento:
Article