ORIGINAL RESEARCH article
Front. Immunol.
Sec. Mucosal Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1580963
Penicillamine Ameliorates Intestinal Barrier Damage in Dextran Sulfate Sodium-Induced Experimental Colitis Mice by Inhibiting Cuproptosis
Provisionally accepted
- 1The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- 2Department of General surgery, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China
- 3Interational Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
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Cuproptosis is a copper-dependent form of cell death. However, its role in ulcerative colitis (UC) remains unknown.Aim: To investigate whether cuproptosis is involved in UC and whether penicillamine (PA) improves colitis in mice by inhibiting cuproptosis.We analyzed the expression of cuproptosis-related genes in patients with UC using the Gene Expression Omnibus database. We used dextran sulfate sodium (DSS) to establish an experimental model of UC and explore the effects of cuproptosis on the intestinal barrier. Mice were treated with the copper-depleting agent tetrathiomolybdate to establish causality between cuproptosis and intestinal barrier damage in mice with DSS-induced colitis. We assessed the effects of PA on the intestinal barrier in mice with DSS-induced colitis. Key methodologies included copper quantification using inductively coupled plasma mass spectrometry and rubeanic acid histochemical staining, along with the analysis of cuproptosis-related and barrier proteins using qRT-PCR, immunoblotting, immunohistochemistry, and immunofluorescence.UC and in DSS-induced colitis mice, characterized by increased copper levels and dihydrolipoamide S-acetyltransferase (DLAT) oligomerization and reduced Fe-S cluster-containing proteins ferredoxin 1 (FDX1) and lipoyl synthase (LIAS) levels.Copper depletion ameliorated disease-related manifestations in mice with colitis, mitigated the aberrant expression of pro-inflammatory factors, and concurrently enhanced the expression of tight junction proteins. PA inhibited cuproptosis in the intestinal barrier of mice with colitis by reducing excess copper levels and DLAT oligomerization, as well as rescuing the loss of FDX1 and LIAS.Cuproptosis is involved in UC pathogenesis. The identification of PA, which inhibits cuproptosis in the intestinal barrier of mice with colitis, provides a novel therapeutic option for the clinical management of UC.
Keywords: ulcerative colitis, inflammatory bowel disease, Penicillamine, cuproptosis, intestinal barrier
Received: 21 Feb 2025; Accepted: 07 Aug 2025.
Copyright: © 2025 Ma, Ma, Wang, Tang, Chen, Li, Chen and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yugen Chen, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
Tuo Chen, Department of General surgery, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China
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