C6orf120 gene deficiency may be vulnerable to carbon tetrachloride induced acute hepatic injury in rats

Abstract

Introduction The function of the C6orf120 gene, which encodes an N-glycosylated protein, remains unknown. The study was performed to characterize the utility of the C6orf120 gene in carbon tetrachloride-induced acute liver injury and to elucidate the potential underlying mechanisms by establishing a C6orf120 gene-knockout (C6orf120 –/– ) rat model. Material and methods C6orf120 -/- and wild-type (WT) rats were intraperitoneally administered with CCl 4 (1 : 1 v/v in olive oil, 2 µl/g). Rats were sacrificed 24 h after CCl 4 administration. Liver tissues were collected for H&E, IHC, qRT-PCR, and Western blot analysis. Results C6orf120 gene deficiency may be vulnerable to CCl 4 -induced acute liver injury in rats as indicated by the high levels of alanine aminotransferase (WT: 388.7 ±55.96 vs. C6orf120 –/– : 915.9 ±118.8, p < 0.001) and greater degree of pathological damage. Quantitative reverse transcription polymerase chain reaction showed that the mRNA levels of inflammation-associated cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-, in liver tissues were increased in C6orf120 –/– rats compared with those in WT rats. Moreover, western blot showed that the protein expression of cytokines nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain containing 3 (NLRP3), caspase-1, IL-1β, nuclear factor-κB, c-Jun N-terminal kinases, and Bax were increased in C6orf120 –/– rats compared with those in WT rats. Conclusions C6orf120 –/– rats were susceptible to CCl 4 -induced liver injury, which may be related to NLRP3 inflammasome and JNK signaling pathway activation.

Keywords

• acute hepatic injury
• c6orf120
• inflammation
• ccl 4
• apoptosis