Chuantao Zhang1, Xiang Cui2, Lian Feng3, Zhiyi Han2, Deti Peng2, Wenjun Fu4, Yufeng Xing2. 1. Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. 2. Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China. 3. The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China. 4. South China Research Center for Acupuncture and Moxibustion, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
Abstract
BACKGROUND: Gut microbiota has a number of essential roles in nutrition metabolism and immune homeostasis, and is closely related to hepatocellular progression. In recent years, studies have also shown that FK506 binding protein 5 (FKBP-5) plays a crucial role in immune regulation. However, it is not yet clear whether FKBP-5 promotes the development of hepatocellular carcinoma (HCC) by affecting immune function and gut microbiota. METHODS: FKBP-5 expression was verified by immunochemistry and western blot and reverse transcription polymerase chain reaction (RT-qPCR) assays. After treatment in WT and FKBP-5-/- mice, the histological characteristic of mice liver tissue was assessed by H&E staining, and hepatic leukocytes and hepatic NKT cells were identified by flow cytometer. Meanwhile, primary bile acids (BAs), secondary BAs, serum total cholesterol, and the weight of abdomen adipose tissues were examined, and the gut microbiota was evaluated by 16S ribosomal ribonucleic acid (rRNA) sequencing. RESULTS: We discovered that FKBP-5 was highly expressed in HCC tissues. Meanwhile, FKBP-5 deletion inhibited tumor progression by increasing CD8+ T, CD4+ T, NKT and CD4+NKT cells in mice after diethylnitrosamine (DEN) injection. Besides, we proved that FKBP-5 deletion generated rapid and significant reductions in the intestinal BAs, the weight of abdomen adipose tissues and the serum total cholesterol. FKBP-5 deletion also led to a change in the composition of gut microbiota, suggesting that BAs are the main dietary factor regulating gut microbiota, which could be affected by FKBP-5 deletion. Further, we uncovered that anti-CD4 and anti-CD8 treatments facilitated hepatocellular progression by modulating gut microbiota composition in FKBP-5-/- mice. CONCLUSIONS: Therefore, we demonstrated that FKBP-5 deletion inhibited hepatocellular progression by modulating immune response and gut microbiome-mediated BAs metabolism. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: Gut microbiota has a number of essential roles in nutrition metabolism and immune homeostasis, and is closely related to hepatocellular progression. In recent years, studies have also shown that FK506 binding protein 5 (FKBP-5) plays a crucial role in immune regulation. However, it is not yet clear whether FKBP-5 promotes the development of hepatocellular carcinoma (HCC) by affecting immune function and gut microbiota. METHODS: FKBP-5 expression was verified by immunochemistry and western blot and reverse transcription polymerase chain reaction (RT-qPCR) assays. After treatment in WT and FKBP-5-/- mice, the histological characteristic of mice liver tissue was assessed by H&E staining, and hepatic leukocytes and hepatic NKT cells were identified by flow cytometer. Meanwhile, primary bile acids (BAs), secondary BAs, serum total cholesterol, and the weight of abdomen adipose tissues were examined, and the gut microbiota was evaluated by 16S ribosomal ribonucleic acid (rRNA) sequencing. RESULTS: We discovered that FKBP-5 was highly expressed in HCC tissues. Meanwhile, FKBP-5 deletion inhibited tumor progression by increasing CD8+ T, CD4+ T, NKT and CD4+NKT cells in mice after diethylnitrosamine (DEN) injection. Besides, we proved that FKBP-5 deletion generated rapid and significant reductions in the intestinal BAs, the weight of abdomen adipose tissues and the serum total cholesterol. FKBP-5 deletion also led to a change in the composition of gut microbiota, suggesting that BAs are the main dietary factor regulating gut microbiota, which could be affected by FKBP-5 deletion. Further, we uncovered that anti-CD4 and anti-CD8 treatments facilitated hepatocellular progression by modulating gut microbiota composition in FKBP-5-/- mice. CONCLUSIONS: Therefore, we demonstrated that FKBP-5 deletion inhibited hepatocellular progression by modulating immune response and gut microbiome-mediated BAs metabolism. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
Entities:
Keywords:
FK506 binding protein 51; bile acids; gut microbiota; hepatocellular carcinoma (HCC); immune cells
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