Integrated network toxicology and experimental validation identify VCAM1 as a candidate molecular link between pyrethroid exposure and keloid.

Authors

Zun Wang, Chen Yang, Wencai Wang, Zijian Zhang, Zhonghua Sun, Zhiyong Diao

Published in

PloS one. Volume 21. Issue 11. Pages e0362474. Epub Nov 10, 2026.

Abstract

Keloids are fibroproliferative skin lesions characterized by excessive extracellular matrix deposition. The potential molecular links between pyrethroid exposure and keloid-associated alterations remain unclear.
We integrated network toxicology, machine learning, single-cell transcriptomics, virtual gene perturbation, molecular docking, molecular dynamics simulation, external transcriptomic validation, and qRT-PCR to investigate candidate molecular links between pyrethroid exposure and keloid.
A total of 127 shared candidate targets between pyrethroid insecticides and keloid were identified, mainly enriched in MAPK, PI3K-Akt, and FoxO signaling pathways. Three machine-learning algorithms prioritized VCAM1 and FGFR1. In GSE145725, both genes showed significant differential expression and high dataset-level discriminatory performance. In the integrated external validation cohort generated from GSE90051 and GSE158395, VCAM1 remained significantly upregulated and showed good discriminatory performance (AUC = 0.869), whereas FGFR1 showed weaker external support (AUC = 0.677) without significant differential expression. Molecular docking and 100-ns molecular dynamics simulation supported the structural plausibility of selected pyrethroid-target interactions, particularly theta-cypermethrin with VCAM1. Single-cell analysis characterized the cell-type-specific distribution of candidate genes, while virtual gene perturbation suggested a putative VCAM1-SOCS3 regulatory relationship. qRT-PCR further showed that 20 μM cypermethrin exposure for 24 h significantly increased VCAM1 mRNA expression in KEL FIB cells.
VCAM1 emerged as the most consistently supported candidate linking cypermethrin exposure with keloid-associated molecular alterations, while the predicted VCAM1-SOCS3 relationship requires further mechanistic validation.

PMID:
43008012
Bibliographic data and abstract were imported from PubMed on 11 Nov 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.