2. Academic Validation
  3. Mechanisms and targeted reversion/prevention of hepatic fibrosis caused by the non-hereditary toxicity of benzo(a)pyrene

Mechanisms and targeted reversion/prevention of hepatic fibrosis caused by the non-hereditary toxicity of benzo(a)pyrene

  • Sci Total Environ. 2023 Dec 21:912:169496. doi: 10.1016/j.scitotenv.2023.169496.
Xinru Du 1,  Ming Jin 1,  Ruzhi Li 2,  Fei Zhou 3,  Yuanze Sun 1,  Qinliang Mo 4,  Sisi Song 1,  Na Dong 5,  Shuoke Duan 1,  Maoxuan Li 1,  Ming Lu 3,  Chi Zhang 3,  Huiwei He 6,  Xiaojun Yang 7,  Chengwu Tang 8,  Yuan Li 9
Affiliations

Affiliations

  • 1 The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
  • 2 The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 3 The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 4 The First Affiliated Hospital of Huzhou University, Huzhou, China.
  • 5 The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China; The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 6 The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
  • 7 The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; Ili & Jiangsu Joint Institute of Health, The Friendship Hospital of Ili Kazakh Autonomous Prefecture, Xinjiang, China. Electronic address: [email protected].
  • 8 The First Affiliated Hospital of Huzhou University, Huzhou, China. Electronic address: [email protected].
  • 9 The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
PMID: 38135085 DOI: 10.1016/j.scitotenv.2023.169496
Abstract

The effect of long term exposure to low concentrations of environmental pollutants on hepatic disorders is a major public health concern worldwide. Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants. In recent years, an increasing number of studies have focused on the deleterious effects of low concentrations of PAHs in the initiation or exacerbation of the progression of chronic liver disease. However, the underlying molecular mechanisms and effective intervention methods remain unclear. Here, we found that in hepatocytes, a low concentration of benzo(a)pyrene (B[a]P, an indicator of PAHs) chronic exposure continuously activated 14-3-3η via an epigenetic accumulation of DNA demethylation. As a "switch like" factor, 14-3-3η activated its downstream PI3K/Akt signal, which in turn promoted vascular endothelial growth factor (VEGF) production and secretion. As the characteristic fibrogenic paracrine factor regulated by B[a]P/14-3-3η, VEGF significantly induced the neovascularization and activation of hepatic stellate cells, leading to the development of hepatic fibrosis. Importantly, targeted 14-3-3η by using its specific inhibitor invented by our lab could prevent B[a]P-induced hepatic fibrosis, and could even reverse existent hepatic fibrosis caused by B[a]P. The present study not only revealed novel mechanisms, but also proposed an innovative approach for the targeted reversion/prevention of the harmful effects of exposure to PAHs on chronic liver disease.

Keywords

14-3-3η; Benzo(a)pyrene; Hepatic fibrosis; Molecular mechanisms; Targeted reversion/prevention.

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