Correspondence on Letter regarding “Both liver parenchymal and non-parenchymal cells express JCAD proteins under various circumstances” Byoung Kuk Jang Clinical and Molecular Hepatology.2024; 30(2): 297. CrossRef
Background/Aims Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet.
Methods Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation.
Result s: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL.
Conclusions JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.
Citations
Citations to this article as recorded by
Features and functional mechanisms of super-enhancers in cardiovascular disorders, cancer, autoimmune diseases and neurodegenerative disorders Zi-Rong Li, Yong-Yan Wang, Chao Zhang, Jin-Sha Shi, Xiao Yu, Ni-Tong Ying, Xiao-Ke Xu, Juan-Juan Li, Tao Guo Cellular Signalling.2026; 138: 112252. CrossRef
Transient receptor potential channel 6 knockout ameliorates hepatic fibrosis by inhibiting the activation and proliferation of hepatic stellate cells Xixi Zeng, Yanhong Liao, Weiyi Cheng Journal of Gastroenterology and Hepatology.2025; 40(1): 294. CrossRef
Hepatic Stellate Cell TM4SF1 Accelerates Hepatic Fibrosis Progression via Interacting With the Tyrosine Kinase c-Src Shenglu Liu, Peng Tan, Jiatong Chen, Zhiwei Huang, Bingyu Ren, Zhonghao Jiang, Boyuan Gu, Wenhao Yu, Lei Sun, Yingjun Chen, Jian Ruan, Wenguang Fu Cellular and Molecular Gastroenterology and Hepatology.2025; 19(10): 101559. CrossRef
JCAD deficiency delayed liver regenerative repair through the Hippo–YAP signalling pathway Li Zhang, Yong‐Yu Yang, Li Xie, Yuan Zhou, Zhenxing Zhong, Jia Ding, Zhong‐Hua Wang, Yu‐Li Wang, Xiu‐Ping Liu, Fa‐Xing Yu, Jian Wu Clinical and Translational Medicine.2024;[Epub] CrossRef
JCAD, a new potential therapeutic target in cholestatic liver disease Byoung Kuk Jang Clinical and Molecular Hepatology.2024; 30(2): 166. CrossRef
Correspondence on Letter regarding “Both liver parenchymal and non-parenchymal cells express JCAD proteins under various circumstances” Byoung Kuk Jang Clinical and Molecular Hepatology.2024; 30(2): 297. CrossRef
Both liver parenchymal and non-parenchymal cells express JCAD protein under various circumstances Li Xie, Li Zhang, Hui Chen, Yong-Yu Yang, Jian Wu Clinical and Molecular Hepatology.2024; 30(2): 279. CrossRef
Background/Aims Acute-on-chronic liver failure (ACLF) is a catastrophic illness. Few studies investigated the prognostic value of vitamin D-binding protein (VDBP) for hepatitis B virus (HBV)-related ACLF (HBV-ACLF) resulted in conflicting results.
Methods Two prospective HBV-ACLF cohorts (n=287 and n=119) were enrolled to assess and validate the prognostic performance of VDBP.
Result s: VDBP levels in the non-survivors were significantly lower than in the survivors (P<0.001). Multivariate Cox regression demonstrated that VDBP was an independent prognostic factor for HBV-ACLF. The VDBP level at admission gradually decreased as the number of failed organs increased (P<0.001), and it was closely related to coagulation failure. The areas under the receiver operating characteristic curve (AUCs) of the Child-Pugh-VDBP and chronic liver failuresequential organ failure assessment (CLIF–SOFA)-VDBP scores were significantly higher than those of Child-Pugh (P<0.001) and CLIF-SOFA (P=0.0013). The AUCs of model for end-stage liver disease (MELD)-VDBP were significantly higher than those of MELD (P= 0.0384) only in the case of cirrhotic HBV-ACLF patients. Similar results were validated using an external multicenter HBV-ACLF cohort. By longitudinal observation, the VDBP levels gradually increased in survivors (P=0.026) and gradually decreased in non-survivors (P<0.001). Additionally, the VDBP levels were found to be significantly decreased in the deterioration group (P=0.012) and tended to be decreased in the fluctuation group (P=0.055). In contrast, they showed a significant increase in the improvement group (P=0.036).
Conclusions The VDBP was a promising prognostic biomarker for HBV-ACLF. Sequential measurement of circulating VDBP shows value for the monitoring of ACLF progression.
Citations
Citations to this article as recorded by
Omics in acute‐on‐chronic liver failure Peng Li, Xi Liang, Jinjin Luo, Jun Li Liver International.2025;[Epub] CrossRef
Deficiency of vitamin D-binding protein exacerbates liver fibrosis by disrupting iron homeostasis via the activation of YAP signaling Qing Zheng, Qingquan Tan, Dan Wang, Yanling Ma, Yanni Zhou, Yonghua Chen, Dan Long, Jiayin Yang, Li Feng Experimental Cell Research.2025; 452(2): 114767. CrossRef
miR-223-3p predicts prognosis of hepatitis B virus-related acute-on-chronic liver failure and is involved in hepatocyte injury via HSP90B1 Feiyue Xie, Qiuping Ren, Jun He, Menghang Wu Hereditas.2025;[Epub] CrossRef
Background/Aims Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. We aimed to investigate the usefulness of a key biomarker, lipocalin-2 (LCN2), for the detection of NASH progression.
Methods A mouse NASH model was established using a high-fat diet and a high-sugar drinking water. Gene expression profile of the NASH model was analyzed using RNA sequencing. Moreover, 360 NAFLD patients (steatosis, 83; NASH, 277), 40 healthy individuals, and 87 patients with alcoholic fatty liver disease were recruited.
Result s: Inflammatory infiltration, focal necrosis in the leaflets, steatosis, and fibrosis were documented in the mouse liver. In total, 504 genes were differentially expressed in the livers of NASH mice, and showed significant functional enrichment in the inflammation-related category. Upregulated liver LCN2 was found to be significantly interactive with various interleukins and toll-like receptors. Serum LCN2 levels were significantly increased in NAFLD patients. Serum LCN2 levels were correlated with steatosis, intralobular inflammation, semiquantitative fibrosis score, and nonalcoholic fatty liver disease activity score. The area under the curve of serum LCN2 was 0.987 with a specificity of 100% and a sensitivity of 93.5% for NASH diagnosis, and 0.977 with almost the same specificity and sensitivity for steatosis.
Conclusions LCN2 might be involved in the transition from NAFL to NASH by mediating inflammation. Serum LCN2 levels might be a novel biomarker for the diagnosis of NASH.
Citations
Citations to this article as recorded by
Mutation of PXR phosphorylation motif at Ser347 disrupts lipid and bile acid homeostasis in diet-induced metabolic dysfunction–associated steatohepatitis in mice Veronia Basaly, Zakiyah R. Henry, Rulaiha E. Taylor, Bo Kong, Ill Yang, Anita Brinker, Zhenning Yang, Peihong Zhou, Laurie B. Joseph, Lauren Aleksunes, Brian Buckley, Masahiko Negishi, Grace L. Guo Drug Metabolism and Disposition.2026; 54(2): 100222. CrossRef
A diet-driven metabolic dysfunction-associated steatohepatitis (MASH) mouse model resembles the corresponding human disease Guilherme Ribeiro Romualdo, Letícia C. Valente, Gabriel P. Bacil, Luana Riechelmann-Casarin, Antônio R. B. da Fonseca, Miguel W. Fornes, Luís F. Barbisan Journal of Molecular Histology.2025;[Epub] CrossRef
Role of Neutrophils in Homeostasis and Diseases Xingyu Chang, Yulin Liu, Junjun Qiu, Keqin Hua MedComm.2025;[Epub] CrossRef
The Role of an Elevated Fibrosis‐4 Index in Neurocognitive Decline and Brain Volume Reduction in Older Adults With Metabolic Dysfunction‐Associated Steatotic Liver Disease Maiko Nagaoka, Katsuya Nagaoka, Naoto Kajitani, Kazuhiro Yoshiura, Yoko Yoshimaru, Takehisa Watanabe, Hiroko Setoyama, Noboru Fujise, Minoru Takebayashi, Yasuhito Tanaka Geriatrics & Gerontology International.2025; 25(12): 1903. CrossRef
Genetic and Molecular Profiling of PLIN5 and LCN2 in Hepatocellular Carcinoma: Implications for Diagnosis and Prognosis Mahsa Sadat Reypour, Bita Moudi, Massoud Houshmand, Seyyedeh Behnaz Motahari International Journal of Infection.2025;[Epub] CrossRef
Dynamic changes and clinical value of lipocalin 2 in liver diseases caused by microbial infections Feng Chen, Shan-Shan Wu, Chao Chen, Cheng Zhou World Journal of Hepatology.2024; 16(2): 177. CrossRef
Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2 Eun-Ho Lee, Jae-Ho Lee, Do-Young Kim, Young-Seung Lee, Yunju Jo, Tam Dao, Kyung Eun Kim, Dae-Kyu Song, Ji Hae Seo, Young-Kyo Seo, Je Kyung Seong, Changjong Moon, Eugene Han, Mi Kyung Kim, Seungwan Ryu, Minsang Shin, Gu Seob Roh, Hye Ra Jung, Timothy F. Os Experimental & Molecular Medicine.2024; 56(4): 1001. CrossRef
The relevance of intestinal barrier dysfunction, antimicrobial proteins and bacterial endotoxin in metabolic dysfunction‐associated steatotic liver disease Ina Bergheim, José María Moreno‐Navarrete European Journal of Clinical Investigation.2024;[Epub] CrossRef
Diagnostic and prognostic value of plasma lipocalin-2 levels in patients with metabolic dysfunction–associated steatotic liver disease Ahmed Mohamed ElGhandour, Nahla Mohamed Teama, Marwa Abdullah Kamal, Ehab Hassan Nashaat, Amani Mohamed Abdel Ghani, Ahmad Abbas Abdo Egyptian Liver Journal.2024;[Epub] CrossRef
Lipocalin-2 levels increase in plasma of non-alcoholic fatty liver disease patients with metabolic syndrome Hirdesh Chawla, Vivek Bhosale, Ravi Misra, Satyendra Kumar Sonkar, Neera Kohli, Naseem Jamal, Shobhit Raj Vimal, Banwari Dangi, Kavita Durgapal, Shail Singh, Mahendra Pal Singh Negi, Ashim Ghatak International Journal of Diabetes in Developing Countries.2023; 43(1): 105. CrossRef
Immune cells and their derived microRNA-enriched extracellular vesicles in nonalcoholic fatty liver diseases: Novel therapeutic targets Liu Yang, Yawen Hao, Joost Boeckmans, Robim M. Rodrigues, Yong He Pharmacology & Therapeutics.2023; 243: 108353. CrossRef
Noninvasive serum biomarkers for liver fibrosis in NAFLD: current and future Tina Reinson, Ryan M. Buchanan, Christopher D. Byrne Clinical and Molecular Hepatology.2023; 29(Suppl): S157. CrossRef
LCN2 contributes to the improvement of nonalcoholic steatohepatitis by 8-Cetylberberine Huan He, Xue Chai, Juan Li, Changsheng Li, Xinran Wu, Xiaoli Ye, Hang Ma, Xuegang Li Life Sciences.2023; 321: 121595. CrossRef
Lipocalin-2 Secreted by the Liver Regulates Neuronal Cell Function Through AKT-Dependent Signaling in Hepatic Encephalopathy Mouse Model Danbi Jo, Yoon Seok Jung, Juhyun Song Clinical Nutrition Research.2023; 12(2): 154. CrossRef
From NAFLD to HCC: Advances in noninvasive diagnosis Qinchen Xu, Maoxiao Feng, Yidan Ren, Xiaoyan Liu, Huiru Gao, Zigan Li, Xin Su, Qin Wang, Yunshan Wang Biomedicine & Pharmacotherapy.2023; 165: 115028. CrossRef
The relationship between Lipocalin-2 level and hepatic steatosis in obese patients with NAFLD after bariatric surgery Jiaqi Chen, Shihui Lei, Yueye Huang, Xiaojuan Zha, Lei Gu, Donglei Zhou, Jun Li, Feng Liu, Nannan Li, Lei Du, Xiu Huang, Ziwei Lin, Le Bu, Shen Qu Lipids in Health and Disease.2022;[Epub] CrossRef
Immune-related pathogenesis and therapeutic strategies of nonalcoholic steatohepatitis Ki Wung Chung, Ye Eun Cho, Seung-Jin Kim, Seonghwan Hwang Archives of Pharmacal Research.2022; 45(4): 229. CrossRef
Bioinformatics analysis reveals the changes of peroxisome proliferator-activated receptor (PPAR) pathway in the development of Marjolin ulcers Cheng Wang, Lin Cheng, Ying Zhang, Xiaozhuo Zhao, Huijun Zhang, Yuming Shen All Life.2022; 15(1): 960. CrossRef
A multi-omic landscape of steatosis-to-NASH progression Liping Xiang, Xiaoyan Li, Yunchen Luo, Bing Zhou, Yuejun Liu, Yao Li, Duojiao Wu, Lijing Jia, Pei-Wu Zhu, Ming-Hua Zheng, Hua Wang, Yan Lu Life Metabolism.2022; 1(3): 242. CrossRef
A Scoping Review on Lipocalin-2 and Its Role in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma Marinela Krizanac, Paola Berenice Mass Sanchez, Ralf Weiskirchen, Anastasia Asimakopoulos International Journal of Molecular Sciences.2021; 22(6): 2865. CrossRef
Role of Neutrophils in the Pathogenesis of Nonalcoholic Steatohepatitis Seonghwan Hwang, Hwayoung Yun, Sungwon Moon, Ye Eun Cho, Bin Gao Frontiers in Endocrinology.2021;[Epub] CrossRef
First
Prev
