SENP1 Attenuates Hypoxia‑reoxygenation Injury in Liver Sinusoid Endothelial Cells by Relying on the HIF‑1α Signaling Pathway.

Liver sinusoidal endothelial cells (LSECs) have an important role in hepatic ischemia-reperfusion injury (I/R), but the specific molecular mechanism of action is unknown. LSEC proliferation is regulated and fenestration is maintained via the Sentrin/SUMO-specific protease 1 (SENP1)/hypoxia-inducible factor-1 alpha (HIF-1 alpha) signaling axis under hypoxic conditions. In the present study, a hypoxia-reoxygenation (H-R) injury model was established using mouse LSECs to explore the relationship between SENP1 and H-R 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 H-R conditions, it was demonstrated that the expression of SENP1 was upregulated by reverse transcription-quantitative polymerase chain reaction and western blotting (WB). In addition, scanning electron microscopy indicated that fenestrae damage was increased, a Cell Counting Kit-8 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, HIF-1 alpha, heme oxygenase and Bcl-2 were downregulated (as demonstrated by WB), while the expression levels of apoptosis-related proteins, cleaved-caspase-3 and Bax, were upregulated. Enzyme-linked immunosorbent assay detection showed that the level of vascular endothelial growth factor in the supernatant decreased and the level of IL-6 and TNF-alpha increased. Following the administration of an HIF-1 alpha 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 H-R injury through the HIF-1 alpha signaling pathway. In conclusion, SENP1 may attenuate H-R injury in LSECs in a HIF-1 alpha signaling pathway-dependent manner.