The acetylation GLI1 affects arsenical-induced renal fibrosis by mediating the Hedgehog signalling pathway

Pinya Liu; Yating Wang; Peiyu Jin; Qing Zhou; Liang Pei; Shuhua Xi

doi:10.1016/j.ecoenv.2025.118676

Ecotoxicology and Environmental Safety (Sep 2025)

The acetylation GLI1 affects arsenical-induced renal fibrosis by mediating the Hedgehog signalling pathway

Pinya Liu,
Yating Wang,
Peiyu Jin,
Qing Zhou,
Liang Pei,
Shuhua Xi

Affiliations

Pinya Liu: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province 110122, China; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning Province 110122, China; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, Shenyang, Liaoning Province 110122, China
Yating Wang: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province 110122, China; Yantai Center for Disease Control and Prevention, Yantai, Shandong Province 264000, China
Peiyu Jin: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province 110122, China; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning Province 110122, China; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, Shenyang, Liaoning Province 110122, China
Qing Zhou: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province 110122, China; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning Province 110122, China; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, Shenyang, Liaoning Province 110122, China
Liang Pei: Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning Province 110122, China; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, Shenyang, Liaoning Province 110122, China; Corresponding authors at: Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning Province 110122, China.
Shuhua Xi: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province 110122, China; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning Province 110122, China; The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, Shenyang, Liaoning Province 110122, China; Corresponding authors at: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province 110122, China.

DOI: https://doi.org/10.1016/j.ecoenv.2025.118676
Journal volume & issue: Vol. 302
p. 118676

Abstract

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Arsenic exposure by drinking water is a key challenge in the field of public health worldwide. Research has found a connection between arsenic exposure and renal fibrosis, yet the mechanisms behind this are still unclear. In this study, rats were exposed to 50 mg/L NaAsO2 or 200 mg/L dimethylarsinic acid (DMA) via drinking water for 12 weeks, and HK-2 cells were treated with 1 μM NaAsO2 for 4 weeks. The results showed that the renal tubular structure was destroyed, renal function was impaired, and fibrosis occurred in renal tissue in arsenic-exposed F344 rats. Arsenic-treated HK-2 cells presented hydroxyproline levels elevating and fibrosis-related proteins expression increasing. In addition, the levels of Hedgehog signaling pathway-related factors SMO, SHH, GLI1, GLI2 were increased and SUFU was decreased in kidneys of arsenic-treated rats and HK-2 cells, indicating that the Hedgehog signaling pathway was triggered. The fibrosis level was reduced in arsenic treated HK-2 cells after interference with the Hedgehog pathway inhibitor. The activity of GLI1, an important factor in the Hedgehog signaling pathway, is regulated by acetylation modifications. Levels of GLI1 acetylation were reduced in arsenic treated HK-2 cells11 Inhibition of deacetylation reduces fibrosis in arsenic-treated HK-2 cells.. In conclusion, the Hedgehog signaling pathway is vital in arsenic-triggered renal fibrogenesis.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

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