Arsenic-induced senescence and EMT in mouse alveolar type II cells: p62-Keap1-Nrf2 loop
In this abstract, arsenic exposure caused senescence and EMT in a mouse alveolar type II cell line and mouse lungs; the p62-Keap1-Nrf2 loop appeared protective in cell experiments. [1]
Automatic summary · not editorially reviewed
The key findings
In MLE-12 mouse alveolar type II cells and mouse lungs, arsenic exposure progressively decreased E-cadherin and increased N-cadherin, with elevated TGF-β and α-SMA. [1]
Arsenic exposure increased SA-β-gal-positive cells, SASP-related gene activity and p16/p21 expression; Nrf2 knockdown worsened these senescence signs and EMT markers, while DMF reversed them. [1]
Disrupting the p62-Keap1 interaction with K67 restored Keap1-mediated Nrf2 suppression and aggravated senescence and EMT; the authors propose the p62-Keap1-Nrf2 loop as a potential therapeutic target. [1]
The source at a glance
- Study type / format
- Preclinical laboratory study (abstract only)
- Population / context
- MLE-12 mouse alveolar type II cells and murine lung tissue exposed to inorganic arsenic
- Summary based on
- Study abstract
- Original publication
- October 5, 2026
Arsenic effects in MLE-12 cells and mouse lungs
The study asked how arsenic exposure leads to lung fibrosis. In MLE-12 cells, a mouse alveolar type II cell line, and in mouse lung tissue, arsenic exposure progressively lowered the epithelial marker E-cadherin and raised the mesenchymal marker N-cadherin. Levels of TGF-β and α-SMA were also elevated. Senescence signs rose too: more SA-β-gal-positive cells, higher activity of SASP-related genes (including Cxcl1, Cxcl11, Cxcl16, Ccl20, Mcp-1, Tgf-β and Gm-csf), and higher p16 and p21.
Supporting source [1]
Nrf2 knockdown and DMF activation in arsenic-exposed cells
Knocking down Nrf2 made senescence worse in arsenic-exposed cells: more SA-β-gal-positive cells, stronger SASP gene expression, higher p16 and p21, and more EMT marker expression. Conversely, treating arsenic-exposed MLE-12 cells with the Nrf2 activator dimethyl fumarate (DMF) markedly reversed senescence, with lower SASP gene, p16 and p21 expression, and attenuated EMT, with restored E-cadherin and reduced N-cadherin and α-SMA. DMF works by modifying Keap1, which disrupts Keap1-mediated Nrf2 degradation and stabilizes Nrf2.
Supporting source [1]
p62-Keap1 disruption worsened senescence and EMT
Pharmacologically disrupting the p62-Keap1 interaction with K67 restored Keap1-mediated suppression of Nrf2 and further aggravated the senescence and EMT phenotypes. The authors conclude that the p62-Keap1-Nrf2 positive feedback loop acts as a protective axis that attenuates arsenic-evoked senescence and EMT in alveolar type II cells, and suggest it as a potential therapeutic target for arsenic-associated pulmonary fibrosis.
Supporting source [1]
How to interpret this
This explainer is based only on the abstract; the full text was not reviewed. Findings come from a mouse cell line and mouse lung tissue, so they do not establish human outcomes or a treatment.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Guo X, Ma X, Qin L, Li Y, Han X, Wang M, Wei X, Gong S, Su W, Cheng D, Jin Y, Shen F, Zhao X, Guo Z, Li J. · europepmc.org · October 5, 2026