Silencing OGFOD1 ameliorates hepatic ischemia-reperfusion injury through abrogating oxidative stress and apoptosis via downregulating SPARC.

Hepatic ischemia-reperfusion injury (HIRI) is a complicated pathological process impacting the prognosis of patients suffering from liver resection and transplantation surgery. 2-oxoglutarate and iron dependent oxygenase domain containing 1 (OGFOD1), a crucial factor involved in protein translation, was highly expressed during HIRI. However, its role as well as underlying mechanism is still unclear. In this study, two datasets from Gene Expression Omnibus database were analyzed and we focused on OGFOD1 which is associated with ischemia-reperfusion. Later, a HIRI rat model and a hypoxia/reoxygenation (H/R) hepatocyte model were established to explore the expression of OGFOD1 and its underlying mechanism. Furthermore, transcriptomics and proteomics were performed to analyze the downstreams of OGFOD1 in H/R hepatocytes. Our results showed that the expression of OGFOD1 in HIRI rats and H/R hepatocytes were higher than negative controls. OGFOD1 silencing ameliorated liver function, reduced hepatocellular apoptosis and mitigated oxidative stress. Later, the combined analysis of transcriptomics and proteomics showed that 5811 mRNAs and 476 proteins were modulated by OGFOD1 silencing and these factors were classified into four classes. Among these factors, secreted protein acidic and rich in cysteine (SPARC) in Class III, with decreased protein level but no-changed mRNA level, caught our eyes. Silencing OGFOD1 decreased the protein level of SPARC, but not its mRNA level. More interestingly, SPARC overexpression rescued the effects of OGFOD1 silencing on apoptosis and oxidative stress in H/R hepatocytes. Totally, OGFOD1 was a vital modulator during HIRI and its downregulation alleviated oxidative stress and apoptosis through declining SPARC protein level.