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<p>Arsenic contamination poses a significant environmental health risk, yet the mechanisms underlying its induction of hepatic fibrosis remain incompletely elucidated.Our previous clinical studies in arsenic poisoning areas found that serum inflammatory factors (such as IL-6, IL-1β, TNF-α) levels were significantly elevated, but there were no significant differences in liver function and fibrosis markers, suggesting that the inflammatory response precedes detectable typical pathological alterations. Established theories suggest that persistent inflammation is a key factor in the initiation of hepatic fibrosis. PINK1, a key initiator of mitophagy, was found to be downregulated in the livers of arsenic-exposed mice.Based on this, we propose a scientific hypothesis: arsenic exposure induces a persistent inflammatory response by inhibiting PINK1/Parkin-mediated mitophagy, thereby driving hepatic stellate cells (HSCs) activation and the fibrosis process. Experimental validation demonstrated that arsenic exposure significantly inhibited the PINK1/Parkin pathway, impaired mitophagy, and upregulated the expression of fibrosis markers and inflammatory factors in both liver tissues and cells. Conversely, PINK1 overexpression reversed these pathological phenotypes. In summary, dysregulation of the PINK1/Parkin pathway is a pivotal mechanism connecting arsenic exposure to chronic inflammation and the initiation of hepatic fibrosis, providing new insights for early recognition and targeted intervention of arsenic-related liver diseases.</p>

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Arsenic Exposure Induces Hepatic Fibrosis and Triggers Early Inflammatory Responses by Inhibiting Hepatic Stellate Cell PINK1/Parkin-Mediated Mitophagy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月2日

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  • Feiyang Wu,
  • Yan Wang,
  • Sheng Li,
  • Zhiyong Xu,
  • Xiaohui Wang,
  • Haijing Yin,
  • Teng Ma,
  • Li Wang

摘要

Arsenic contamination poses a significant environmental health risk, yet the mechanisms underlying its induction of hepatic fibrosis remain incompletely elucidated.Our previous clinical studies in arsenic poisoning areas found that serum inflammatory factors (such as IL-6, IL-1β, TNF-α) levels were significantly elevated, but there were no significant differences in liver function and fibrosis markers, suggesting that the inflammatory response precedes detectable typical pathological alterations. Established theories suggest that persistent inflammation is a key factor in the initiation of hepatic fibrosis. PINK1, a key initiator of mitophagy, was found to be downregulated in the livers of arsenic-exposed mice.Based on this, we propose a scientific hypothesis: arsenic exposure induces a persistent inflammatory response by inhibiting PINK1/Parkin-mediated mitophagy, thereby driving hepatic stellate cells (HSCs) activation and the fibrosis process. Experimental validation demonstrated that arsenic exposure significantly inhibited the PINK1/Parkin pathway, impaired mitophagy, and upregulated the expression of fibrosis markers and inflammatory factors in both liver tissues and cells. Conversely, PINK1 overexpression reversed these pathological phenotypes. In summary, dysregulation of the PINK1/Parkin pathway is a pivotal mechanism connecting arsenic exposure to chronic inflammation and the initiation of hepatic fibrosis, providing new insights for early recognition and targeted intervention of arsenic-related liver diseases.