Exploring the dermotoxicity of the mycotoxin deoxynivalenol: combined morphologic and proteomic profiling of human epidermal cells reveals alteration of lipid biosynthesis machinery and membrane structural integrity relevant for skin barrier function.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33890134", "kind": "science-record", "revision": 7, "content_hash": "sha256:74d74969b94685b30519bcc6478b15f99117def400be1ec6f736f4c33a540a6b", "created_at": "2026-11-01T15:41:33Z", "updated_at": "2026-11-01T22:03:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring the dermotoxicity of the mycotoxin deoxynivalenol: combined morphologic and proteomic profiling of human epidermal cells reveals alteration of lipid biosynthesis machinery and membrane structural integrity relevant for skin barrier function.", "doi": "10.1007/s00204-021-03042-y", "pmid": "33890134", "authors": ["Giorgia Del Favero", "Lukas Janker", "Benjamin Neuditschko", "Julia Hohenbichler", "Endre Kiss", "Lydia Woelflingseder", "Christopher Gerner", "Doris Marko"], "journal": "Archives of toxicology", "year": 2021, "abstract": "Deoxynivalenol (vomitoxin, DON) is a secondary metabolite produced by Fusarium spp. fungi and it is one of the most prevalent mycotoxins worldwide. Crop infestation results not only in food and feed contamination, but also in direct dermal exposure, especially during harvest and food processing. To investigate the potential dermotoxicity of DON, epidermoid squamous cell carcinoma cells A431 were compared to primary human neonatal keratinocytes (HEKn) cells via proteome/phosphoproteome profiling. In A431 cells, 10 µM DON significantly down-regulated ribosomal proteins, as well as mitochondrial respiratory chain elements (OXPHOS regulation) and transport proteins (TOMM22; TOMM40; TOMM70A). Mitochondrial impairment was reflected in altered metabolic competence, apparently combined with interference of the lipid biosynthesis machinery. Functional effects on the cell membrane were confirmed by live cell imaging and membrane fluidity assays (0.1-10 µM DON). Moreover, a common denominator for both A431 and HEKn cells was a significant downregulation of the squalene synthase (FDFT1). In sum, proteome alterations could be traced back to the transcription factor Klf4, a crucial regulator of skin barrier function. Overall, these results describe decisive molecular events sustaining the capability of DON to impair skin barrier function. Proteome data generated in the study are fully accessible via ProteomeXchange with the accession numbers PXD011474 and PXD013613.", "claims": [{"id": "claim-method", "statement": "Changes in protein abundance values between treated and untreated cells were determined by a two-sided t test with an FDR < 0.05 and setting S0 (x-value of the hyperbolic tangent of the function separating significant events) to 0.1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33890134", "locator": "sections[8] \"MS data processing\" paragraph 2", "quote": "Changes in protein abundance values between treated and untreated cells were determined by a two-sided t test with an FDR < 0.05 and setting S0 (x-value of the hyperbolic tangent of the function separating significant events) to 0.1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data comprising cytoplasmic fraction of DON-treated (10 µM) and untreated A431 cells as well as nuclear extracts (all experimental conditions) have been deposited to the ProteomeXchange Consortium via the PRIDE (Vizcaino et al. 2016) partner repository with the dataset identifier PXD011474. The data obtained with HEKn cells (all experimental conditions) were archived with the identifier PXD013613. Data describing the concentration-dependent effect of DON on the cytoplasmic compartment of A431 cells have been deposited previously with identifier PXD008996 and (Del Favero et al. 2018a). All data are available at http://www.proteomexchange.org/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33890134", "locator": "sections[28] \"notes\" paragraph 1", "quote": "The mass spectrometry proteomics data comprising cytoplasmic fraction of DON-treated (10 µM) and untreated A431 cells as well as nuclear extracts (all experimental conditions) have been deposited to the ProteomeXchange Consortium via the PRIDE (Vizcaino et al. 2016) partner repository with the dataset identifier PXD011474. The data obtained with HEKn cells (all experimental conditions) were archived with the identifier PXD013613. Data describing the concentration-dependent effect of DON on the cytoplasmic compartment of A431 cells have been deposited previously with identifier PXD008996 and (Del Favero et al. 2018a). All data are available at http://www.proteomexchange.org/."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33890134"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD008996"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD008996"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33890134", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s00204-021-03042-y", "sha256": "sha256:f6d9667ed6c3aa5a978547173830a5de2a2f6c213c68b8b17e68eaea097a3224", "bytes": 58250, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s00204-021-03042-y", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8166681", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD008996", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD008996", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD008996", "version": null, "note": "The mass spectrometry proteomics data comprising cytoplasmic fraction of DON-treated (10 µM) and untreated A431 cells as well as nuclear extracts (all experimental conditions) have been deposited to the ProteomeXchange Consortium via the PRIDE (Vizcaino et al. 2016) partner repository with the dataset identifier PXD011474. The data obtained with HEKn cells (all experimental conditions) were archived with the identifier PXD013613. Data describing the concentration-dependent effect of DON on the cytoplasmic compartment of A431 cells have been deposited previously with identifier PXD008996 and (Del Favero et al. 2018a). All data are available at http://www.proteomexchange.org/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The mass spectrometry proteomics data comprising cytoplasmic fraction of DON-treated (10 µM) and untreated A431 cells as well as nuclear extracts (all experimental conditions) have been deposited to the ProteomeXchange Consortium via the PRIDE (Vizcaino et al. 2016) partner repository with the dataset identifier PXD011474. The data obtained with HEKn cells (all experimental conditions) were archived with the identifier PXD013613. Data describing the concentration-dependent effect of DON on the cytoplasmic compartment of A431 cells have been deposited previously with identifier PXD008996 and (Del Favero et al. 2018a). All data are available at http://www.proteomexchange.org/.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Impact of biomechanical stimulation in the toxicity of deoxynivalenol in A431 cells: impairment of “dynamic” cell functions", "resolution_checked_at": "2026-10-31T18:35:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:PXD011474", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD011474", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD011474", "version": null, "note": "The mass spectrometry proteomics data comprising cytoplasmic fraction of DON-treated (10 µM) and untreated A431 cells as well as nuclear extracts (all experimental conditions) have been deposited to the ProteomeXchange Consortium via the PRIDE (Vizcaino et al. 2016) partner repository with the dataset identifier PXD011474. The data obtained with HEKn cells (all experimental conditions) were archived with the identifier PXD013613. Data describing the concentration-dependent effect of DON on the cytoplasmic compartment of A431 cells have been deposited previously with identifier PXD008996 and (Del Favero et al. 2018a). All data are available at http://www.proteomexchange.org/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The mass spectrometry proteomics data comprising cytoplasmic fraction of DON-treated (10 µM) and untreated A431 cells as well as nuclear extracts (all experimental conditions) have been deposited to the ProteomeXchange Consortium via the PRIDE (Vizcaino et al. 2016) partner repository with the dataset identifier PXD011474. The data obtained with HEKn cells (all experimental conditions) were archived with the identifier PXD013613. Data describing the concentration-dependent effect of DON on the cytoplasmic compartment of A431 cells have been deposited previously with identifier PXD008996 and (Del Favero et al. 2018a). All data are available at http://www.proteomexchange.org/.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Deoxynivalenol and A431 epidermoid squamous carcinoma cells: proteomic profiling reveals the pathways connecting ribosomal inhibition with the loss of function of the cell membrane", "resolution_checked_at": "2026-10-31T18:35:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:PXD013613", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD013613", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD013613", "version": null, "note": "The mass spectrometry proteomics data comprising cytoplasmic fraction of DON-treated (10 µM) and untreated A431 cells as well as nuclear extracts (all experimental conditions) have been deposited to the ProteomeXchange Consortium via the PRIDE (Vizcaino et al. 2016) partner repository with the dataset identifier PXD011474. The data obtained with HEKn cells (all experimental conditions) were archived with the identifier PXD013613. Data describing the concentration-dependent effect of DON on the cytoplasmic compartment of A431 cells have been deposited previously with identifier PXD008996 and (Del Favero et al. 2018a). All data are available at http://www.proteomexchange.org/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The mass spectrometry proteomics data comprising cytoplasmic fraction of DON-treated (10 µM) and untreated A431 cells as well as nuclear extracts (all experimental conditions) have been deposited to the ProteomeXchange Consortium via the PRIDE (Vizcaino et al. 2016) partner repository with the dataset identifier PXD011474. The data obtained with HEKn cells (all experimental conditions) were archived with the identifier PXD013613. Data describing the concentration-dependent effect of DON on the cytoplasmic compartment of A431 cells have been deposited previously with identifier PXD008996 and (Del Favero et al. 2018a). All data are available at http://www.proteomexchange.org/.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Deoxynivalenol and human epidermal cells: proteomic profiling indicates alterations of cell membrane integrity and barrier function", "resolution_checked_at": "2026-10-31T18:35:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:PXD008996 not downloaded", "asset:data:geo:PXD008996 licence not read", "asset:data:geo:PXD011474 not downloaded", "asset:data:geo:PXD011474 licence not read", "asset:data:geo:PXD013613 not downloaded", "asset:data:geo:PXD013613 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-2", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "PCA"}}, {"id": "method-3", "family": null, "specific": null, "label": "Two-sided t test with permutation-based false discovery rate correction (FDR < 0.05)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Changes in protein abundance values between treated and untreated cells were determined by a two-sided t test with an FDR < 0.05 and setting S0 (x-value of the hyperbolic tangent of the function separating significant events) to 0.1."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["PXD011474", "PXD013613", "PXD008996"], "resolved_accessions": ["PXD011474", "PXD013613", "PXD008996"], "statements": ["The mass spectrometry proteomics data comprising cytoplasmic fraction of DON-treated (10 µM) and untreated A431 cells as well as nuclear extracts (all experimental conditions) have been deposited to the ProteomeXchange Consortium via the PRIDE (Vizcaino et al. 2016) partner repository with the dataset identifier PXD011474. The data obtained with HEKn cells (all experimental conditions) were archived with the identifier PXD013613. Data describing the concentration-dependent effect of DON on the cytoplasmic compartment of A431 cells have been deposited previously with identifier PXD008996 and (Del Favero et al. 2018a). All data are available at http://www.proteomexchange.org/."], "basis": "The paper names PXD011474, PXD013613, PXD008996 in ProteomeXchange Consortium via the PRIDE partner repository and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:33890134", "data:geo:PXD008996"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD008996"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:29:21Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 42063, "completion_tokens": 1478, "cached_tokens": 784}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:33890134", "type": "paper", "label": "pmid:33890134"}, {"id": "source:pmid:33890134", "type": "manuscript", "label": "PMID 33890134 full text"}, {"id": "data:geo:PXD008996", "type": "dataset", "label": "GEO PXD008996"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33890134", "type": "paper", "label": "pmid:33890134"}, {"id": "source:pmid:33890134", "type": "manuscript", "label": "PMID 33890134 full text"}, {"id": "data:geo:PXD008996", "type": "dataset", "label": "GEO PXD008996"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33890134", "type": "extraction", "used": ["source:pmid:33890134"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD008996", "type": "accession_resolution", "used": ["data:geo:PXD008996"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:33890134", "parent_hash": "sha256:afceff257a0bda68bcd5545d52bd4536854a56136ae3823ba3f5e9e1d3e11ea4", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:PXD008996 licence not read", "asset:data:geo:PXD008996 not downloaded", "asset:data:geo:PXD011474 licence not read", "asset:data:geo:PXD011474 not downloaded", "asset:data:geo:PXD013613 licence not read", "asset:data:geo:PXD013613 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["ANOVA"], "order_basis": "analysis_only", "id": "assay:1"}]}