2. Academic Validation
  3. Curcumol inhibits KLF5-dependent angiogenesis by blocking the ROS/ERK signaling in liver sinusoidal endothelial cells

Curcumol inhibits KLF5-dependent angiogenesis by blocking the ROS/ERK signaling in liver sinusoidal endothelial cells

  • Life Sci. 2021 Jan 1;264:118696. doi: 10.1016/j.lfs.2020.118696.
Liyuan Gao 1,  Xiang Yang 1,  Yang Li 1,  Zhenyi Wang 1,  Shijun Wang 2,  Shanzhong Tan 3,  Anping Chen 4,  Peng Cao 5,  Jiangjuan Shao 6,  Zili Zhang 6,  Feng Zhang 7,  Shizhong Zheng 8
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
  • 2 Shandong Co-innovation Center of TCM Formula, College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
  • 3 Department of Integrated TCM and Western Medicine, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
  • 4 Department of Pathology, School of Medicine, Saint Louis University, St Louis, USA.
  • 5 Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
  • 6 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
  • 7 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: 300631@njucm.edu.cn.
  • 8 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: nytws@163.com.
PMID: 33157090 DOI: 10.1016/j.lfs.2020.118696
Abstract

Aims: Liver fibrosis is a difficult problem in the medical field. We previously reported that curcumol, a bioactive substance, may inhibit the pathological angiogenesis of liver sinusoidal endothelial cells (LSECs) and play a good anti-hepatic fibrosis effect. However, the mechanism of curcumol inhibiting angiogenesis in LSEC needs to be further clarified. Here, we focus on how curcumol inhibits LSEC angiogenesis in liver fibrosis.

Materials and methods: Primary rat LSECs were cultured in vitro, and various molecular experiments including Real-Time PCR, western blot, immunofluorescence, tube formation assay and transwell migration assay were used to clarify the potential mechanism of curcumol. Carbon tetrachloride (CCl4) was applied to create a mouse liver fibrosis model. Blood and livers were taken to elucidate the efficacy of curcumol in vivo.

Key findings: We found that curcumol could effectively inhibit LSEC angiogenesis in vitro. Interestingly, this process may depend on curcumol's inhibition of the expression of transcription factor KLF5. Mice experiment also showed that curcumol could alleviate chronic liver injury by reducing KLF5 expression. In addition, we suggested that curcumol could reduce the production of mitochondrial ROS and improve mitochondrial morphology in LSEC. More importantly, we proved that curcumol could suppress KLF5-mediated LSEC angiogenesis by inhibiting ROS/ERK signaling.

Significance: We suggested that transcription factor KLF5 could be considered as a new target molecule of curcumol in improving liver fibrosis, and pointed out that curcumol targeted ROS/ERK-mediated KLF5 expression could inhibit LSEC angiogenesis. This provided a new theoretical basis for curcumol to ameliorate liver fibrosis.

Keywords

Angiogenesis; Curcumol; ERK; KLF5; Liver sinusoidal endothelial cells; ROS.

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