Carbon tetrachloride does not promote hepatic fibrosis in ob/ob mice via downregulation of lipocalin-2 protein
Hyun Joo Shin,
Kyung Eun Kim,
Hyeong Seok An,
Eun Ae Jeong,
Jiwon Oh,
Yundong Sun,
Dong-Ju Park,
Jaewoong Lee,
Jinsung Yang,
Gu Seob Roh
Affiliations
Hyun Joo Shin
Department of Anatomy and Convergence Medical Science, College of Medicine, Metabolic Dysfunction Liver Disease Research Center, Institute of Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea
Kyung Eun Kim
Department of Anatomy and Convergence Medical Science, College of Medicine, Metabolic Dysfunction Liver Disease Research Center, Institute of Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea
Hyeong Seok An
Department of Anatomy and Convergence Medical Science, College of Medicine, Metabolic Dysfunction Liver Disease Research Center, Institute of Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea
Eun Ae Jeong
Department of Anatomy and Convergence Medical Science, College of Medicine, Metabolic Dysfunction Liver Disease Research Center, Institute of Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea
Jiwon Oh
Department of Anatomy and Convergence Medical Science, College of Medicine, Metabolic Dysfunction Liver Disease Research Center, Institute of Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea
Yundong Sun
Department of Anatomy and Convergence Medical Science, College of Medicine, Metabolic Dysfunction Liver Disease Research Center, Institute of Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea
Dong-Ju Park
Department of Anatomy and Convergence Medical Science, College of Medicine, Metabolic Dysfunction Liver Disease Research Center, Institute of Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea
Jaewoong Lee
Department of Anatomy and Convergence Medical Science, College of Medicine, Metabolic Dysfunction Liver Disease Research Center, Institute of Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea
Jinsung Yang
Department of Biochemistry, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea
Gu Seob Roh
Department of Anatomy and Convergence Medical Science, College of Medicine, Metabolic Dysfunction Liver Disease Research Center, Institute of Medical Science, Gyeongsang National University, Jinju, 52727, Republic of Korea; Corresponding author. Department of Anatomy, College of Medicine, Gyeongsang National University, 15, Jinju-daero 816 Beon-gil, Jinju-si, Gyeongnam, 52727, Republic of Korea.
Although leptin-deficient ob/ob mice have been investigated to determine whether hepatic steatosis promotes susceptibility to hepatotoxic insults, carbon tetrachloride (CCl4)-induced hepatic fibrosis in ob/ob mice remains largely unknown. In this study, we evaluate the pathogenic mechanisms of hepatic fibrosis in CCl4-treated wild-type (WT) and ob/ob mice and analyze some parameters related to lipogenesis, inflammation, fibrosis, oxidative stress, apoptosis, and autophagy. CCl4 treatment attenuated liver weight and lipogenesis in ob/ob mice. Increased hepatic fibrosis-related proteins were reduced in CCl4-treated ob/ob mice compared with CCl4-treated WT mice. Specifically, the expression of lipocalin-2 (LCN2) was markedly reduced in CCl4-treated ob/ob mice versus CCl4-treated WT mice. Compared with CCl4-treated WT mice, CCl4-treated ob/ob mice had reduced expression of neutrophil-related inflammatory genes and proteins. Hepatic heme oxygenase-1 protein was reduced in CCl4-treated ob/ob mice compared with CCl4-treated WT mice. However, CCl4 did not promote hepatic apoptosis in ob/ob mice. Therefore, these findings highlight LCN2 as a key signaling factor in CCl4-induced hepatic fibrosis.
