Smurf1 Facilitates Oxidative Stress and Fibrosis of Ligamentum Flavum by Promoting Nrf2 Ubiquitination and Degradation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37091902", "kind": "science-record", "revision": 4, "content_hash": "sha256:1334ccba45e90e5ecb1c00b28fb4558253872a9b82b1ff6145d35587c046bc57", "created_at": "2026-11-01T19:01:45Z", "updated_at": "2026-11-01T22:51:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Smurf1 Facilitates Oxidative Stress and Fibrosis of Ligamentum Flavum by Promoting Nrf2 Ubiquitination and Degradation.", "doi": "10.1155/2023/1164147", "pmid": "37091902", "authors": ["Yifei Gu", "Jinquan Hu", "Chen Wang", "Min Qi", "Yu Chen", "Wenchao Yu", "Zhanchao Wang", "Xinwei Wang", "Wen Yuan"], "journal": "Mediators of inflammation", "year": 2023, "abstract": "Lumbar spinal stenosis (LSS), which can lead to irreversible neurologic damage and functional disability, is characterized by hypertrophy and fibrosis in the ligamentum flavum (LF). However, the underlying mechanism is still unclear. In the current study, the effect of Smurf1, a kind of E3 ubiquitin ligase, in promoting the fibrosis and oxidative stress of LF was investigated, and its underlying mechanism was explored. The expression of oxidative stress and fibrosis-related markers was assessed in the tissue of lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH). Next, the expression of the top 10 E3 ubiquitin ligases, obtained from Gene Expression Omnibus (GEO) dataset GSE113212, was assessed in LDH and LSS, and confirmed that Smurf1 expression was markedly upregulated in the LSS group. Furthermore, Smurf1 overexpression promotes the fibrosis and oxidative stress of LF cells. Subsequently, NRF2, an important transcription factor for oxidative stress and fibrosis, was predicted to be a target of Smurf1. Mechanistically, Smurf1 directly interacts with Nrf2 and accelerates Nrf2 ubiquitination and degradation. In conclusion, the current study suggests that Smurf1 facilitated the fibrosis and oxidative stress of LF and induced the development of LSS by promoting Nrf2 ubiquitination and degradation.", "claims": [{"id": "claim-method", "statement": "The student's t-test was used to assess the significance between two groups, and more than two groups was determined by one-way ANOVA followed by Tukey-Kramer multiple comparisons test was applied to determine the data for more than two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37091902", "locator": "sections[13] \"2.11. Statistical Analysis\" paragraph 2", "quote": "The student's t-test was used to assess the significance between two groups, and more than two groups was determined by one-way ANOVA followed by Tukey-Kramer multiple comparisons test was applied to determine the data for more than two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data used to support the study's findings is given in the article's figures.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37091902", "locator": "sections[23] \"Data Availability\" paragraph 2", "quote": "The raw data used to support the study's findings is given in the article's figures."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "", "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:37091902"], "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:GSE113212"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE113212"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37091902", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2023/1164147", "sha256": "sha256:c6ae8a342657b1d117663ba9c3f7f35877b8c7d6e4941053938ad1d8da98e900", "bytes": 32939, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2023/1164147", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10118886", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE113212", "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=GSE113212", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE113212", "version": null, "note": "The raw data used to support the study's findings is given in the article's figures.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The raw data used to support the study's findings is given in the article's figures.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3100386", "GSM3100387", "GSM3100388", "GSM3100389", "GSM3100390", "GSM3100391", "GSM3100392", "GSM3100393"], "sample_count": 8, "group_sizes": null, "group_sizes_basis": null, "platform": "17077", "taxon": "Homo sapiens", "title": "The hypertrophy of the ligamentum flavum is assosciated with activation of the unfolded protein respone", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE113212 not downloaded", "asset:data:geo:GSE113212 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The student's t-test was used to assess the significance between two groups, and more than two groups was determined by one-way ANOVA followed by Tukey-Kramer multiple comparisons test was applied to determine the data for more than two groups."}}, {"id": "method-2", "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"}}], "targets": [], "gaps": ["method.student_t"]}, "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": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "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": ["GSE113212"], "resolved_accessions": ["GSE113212"], "statements": ["The raw data used to support the study's findings is given in the article's figures."], "basis": "The paper names GSE113212 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:37091902", "data:geo:GSE113212"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE113212"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:37:26Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11019, "completion_tokens": 1377, "cached_tokens": 264}}, "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:37091902", "type": "paper", "label": "pmid:37091902"}, {"id": "source:pmid:37091902", "type": "manuscript", "label": "PMID 37091902 full text"}, {"id": "data:geo:GSE113212", "type": "dataset", "label": "GEO GSE113212"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37091902", "type": "paper", "label": "pmid:37091902"}, {"id": "source:pmid:37091902", "type": "manuscript", "label": "PMID 37091902 full text"}, {"id": "data:geo:GSE113212", "type": "dataset", "label": "GEO GSE113212"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37091902", "type": "extraction", "used": ["source:pmid:37091902"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE113212", "type": "accession_resolution", "used": ["data:geo:GSE113212"], "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:37091902", "parent_hash": "sha256:32c9bbbdb91a4593e46c45d20d700cf795808e46f94c6aaf4266fae94929e820", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE113212 licence not read", "asset:data:geo:GSE113212 not downloaded", "execution.not_run", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["n III, and α-SMA was assessed by qRT-PCR and western blotting in the LF tissues of HLF and LDH. We found t", "protein expression was further confirmed by western blotting and IHC. Similar to the qRT-PCR results, wes", "ing and IHC. Similar to the qRT-PCR results, western blotting and IHC data showed that the expressions of", "group (n = 27). ∗p < 0.05. ∗∗∗p < 0.001. (c) Western blotting and semiquantification for Smurf1 expression"], "order_basis": "paper_text_order:3586", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["F and LDH groups (n = 10). ∗∗∗p < 0.001. (d) Immunohistochemistry for Smurf1 expression in the HLF and LDH gro", "oreover, the result was further confirmed by IHC staining (Figure 1(d)). Given that oxidative", "LF patients was assessed by western-blot and IHC (n = 10). ∗∗p < 0.01, ∗∗∗p < 0.001. Oxidativ", "as further confirmed by western blotting and IHC. Similar to the qRT-PCR results, western blo"], "order_basis": "paper_text_order:3816", "id": "assay:2"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["pression in the HLF group were determined by ELISA. Figures 2(a) and 2(b) showed that the MDA c"], "order_basis": "paper_text_order:3993", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The student's t-test was used to assess the significance between two groups, and more than two groups was determined by one-way ANOVA followed by Tukey-Kramer multiple comparisons test was applied to determine the data for more than two groups."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}