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ShanghaiTech University Knowledge Management System
Characterizing disease progression of nonalcoholic steatohepatitis in Leptin-deficient rats by integrated transcriptome analysis | |
2021-03 | |
发表期刊 | EXPERIMENTAL BIOLOGY AND MEDICINE (IF:2.8[JCR-2023],3.5[5-Year]) |
ISSN | 1535-3702 |
EISSN | 1535-3699 |
卷号 | 246期号:6页码:678-687 |
发表状态 | 已发表 |
DOI | 10.1177/1535370220976530 |
摘要 | Nonalcoholic steatohepatitis (NASH) is an aggressive liver disease threatening human health, yet no medicine is developed to treat this disease. In this study, we first discovered that Leptin mutant rats (Lep(Delta I14/Delta I14)) exhibit characteristic NASH phenotypes including steatosis, lymphocyte infiltration, and ballooning after postnatal week 16. We then examined NASH progression by performing an integrated analysis of hepatic transcriptome in Leptin-deficient rats from postnatal 4 to 48 weeks. Initially, simple steatosis in Lep(Delta I14/Delta I14) rats were observed with increased expression of the genes encoding for rate-limiting enzymes in lipid metabolism such as acetyl-CoA carboxylase and fatty acid synthase. When NASH phenotypes became well developed at postnatal week 16, we found gene expression changes in insulin resistance, inflammation, reactive oxygen species and endoplasmic reticulum stress. As NASH phenotypes further progressed with age, we observed elevated expression of cytokines and chemokines including C-C motif chemokine ligand 2, tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta together with activation of the c-Jun N-terminal kinase and nuclear factor-kappa B pathways. Histologically, livers in Lep(Delta I14/Delta I14) rats exhibited increased cell infiltration of MPO+ neutrophils, CD8(+) T cells, CD68(+) hepatic macrophages, and CCR2(+) inflammatory monocyte-derived macrophages associated with macrophage polarization from M2 to M1. Subsequent cross-species comparison of transcriptomes in human, rat, and mouse NASH models indicated that Leptin-deficient rats bear more similarities to human NASH patients than previously established mouse NASH models. Taken together, our study suggests that Lep(Delta I14/Delta I14) rats are a valuable pre-clinical rodent model to evaluate NASH drug safety and efficacy. |
关键词 | Nonalcoholic steatohepatitis transcriptome hepatic inflammation animal model |
收录类别 | SCI ; SCIE |
语种 | 英语 |
WOS研究方向 | Medicine, Research & Experimental |
WOS类目 | Research & Experimental Medicine |
WOS记录号 | WOS:000628236400005 |
出版者 | SAGE PUBLICATIONS LTD |
原始文献类型 | Article |
引用统计 | 正在获取...
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文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/126103 |
专题 | 免疫化学研究所 免疫化学研究所_公共科研平台_生物医学大数据平台 免疫化学研究所_特聘教授组_范国平组 |
通讯作者 | Fan, Guoping; Zhu, Xianmin |
作者单位 | 1.Tongji Univ, Sch Med, Tongji Stem Cell Res Ctr, Shanghai 200092, Peoples R China; 2.Tongji Univ, Translat Ctr Stem Cell Res, Tongji Hosp, Dept Regenerat Med,Sch Med, Shanghai 200065, Peoples R China; 3.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Sch Life Sci & Technol, Inst Translat Res,Tongji Hosp, Shanghai 200092, Peoples R China; 4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China; 5.Tongji Univ, Sch Med, Shanghai Pulm Hosp, Shanghai 200433, Peoples R China; 6.Guangdong Inst Appl Biol Resources, Guangdong Publ Lab Wild Anim Conservat & Utilizat, Guangdong Key Lab Anim Conservat & Resource Utili, Guangzhou 510260, Peoples R China; 7.Tongji Univ, Tsingtao Adv Res Inst, Res Ctr Stem Cells & Ageing, Tsingdao 266071, Peoples R China; 8.Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA |
通讯作者单位 | 免疫化学研究所 |
推荐引用方式 GB/T 7714 | Lu, Ping,Yang, Guang,Jiang, Lichun,et al. Characterizing disease progression of nonalcoholic steatohepatitis in Leptin-deficient rats by integrated transcriptome analysis[J]. EXPERIMENTAL BIOLOGY AND MEDICINE,2021,246(6):678-687. |
APA | Lu, Ping.,Yang, Guang.,Jiang, Lichun.,He, Wen.,Wu, Wanwan.,...&Zhu, Xianmin.(2021).Characterizing disease progression of nonalcoholic steatohepatitis in Leptin-deficient rats by integrated transcriptome analysis.EXPERIMENTAL BIOLOGY AND MEDICINE,246(6),678-687. |
MLA | Lu, Ping,et al."Characterizing disease progression of nonalcoholic steatohepatitis in Leptin-deficient rats by integrated transcriptome analysis".EXPERIMENTAL BIOLOGY AND MEDICINE 246.6(2021):678-687. |
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