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Updated: Sep 27, 2026
Imaging Approaches to Assessments of Toxicological Oxidative Stress Using Genetically-encoded Fluorogenic Sensors
Published on: February 7, 2018
Network-guided multi-omics characterizes stress-associated transcriptional and metabolic alterations in PFOA-exposed
Yiwei Shang1, Qikai Luo1, Yourou Zhou1
1Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, PR China; Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease, Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology, Zhejiang Chinese Medical University Integrated Research and Clinical Laboratory for Precision Prevention and Treatment of Metabolic and Kidney Diseases, Hangzhou, Zhejiang, 310006, PR China.
Abstract:
Perfluorooctanoic acid (PFOA) is a persistent per- and polyfluoroalkyl substance that undergoes active renal handling, yet the molecular response of proximal tubular cells remains poorly resolved. We integrated network toxicology with matched RNA sequencing and untargeted LC-MS metabolomics in PFOA-exposed HK-2 cells, then compared the resulting model with an external rat kidney transcriptome, public perturbation signatures and cellular assays. The network analysis yielded 657 kidney-relevant candidates. RNA sequencing identified 407 upregulated and 443 downregulated genes, with induction of ATF4-DDIT3-TRIB3 and redox-related genes and repression of E2F, G2-M, mitotic-spindle and DNA-replication programs. Annotation-audited metabolomics retained 61 exploratory responsive features (7 increased and 54 decreased), showing nominal shifts involving nucleotide, amino-acid and carbon-energy intermediates. Cross-platform prioritization highlighted TRIB3, CDKN1A, SLC7A11, ATF3, DDIT3, HMOX1 and SQSTM1. External WGCNA and perturbation-signature analyses showed partial transcriptomic concordance with the main stress, metabolic and cell-cycle patterns. In concentration-group validation experiments, PFOA increased apoptosis, G0/G1 accumulation and lipid peroxidation, lowered EdU incorporation and the GSH/GSSG ratio, and induced the prioritized genes. These data define a PFOA-responsive proximal-tubule stress program accompanied by redox imbalance, exploratory metabolic shifts and proliferative restraint.
