Tideglusib promotes wound healing in aged skin by activating PI3K/Akt pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35729652", "kind": "science-record", "revision": 5, "content_hash": "sha256:70c02bbd31d9ef574b4512139f8e755d289cc2b0552dee5db8203af7776232bb", "created_at": "2026-11-01T18:14:45Z", "updated_at": "2026-11-01T22:49:22Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Tideglusib promotes wound healing in aged skin by activating PI3K/Akt pathway.", "doi": "10.1186/s13287-022-02949-2", "pmid": "35729652", "authors": ["Jiachen Sun", "Hongqing Zhao", "Chuan'an Shen", "Shiyi Li", "Wen Zhang", "Jinglong Ma", "Zhisheng Li", "Ming Zhang", "Jianqiu Yang"], "journal": "Stem cell research & therapy", "year": 2022, "abstract": "BACKGROUND: Aging disturbs the skin morphology and function, manifested as thinned epithelium and impaired wound healing. As a major type of skin cells, epidermal stem cells (EpiSCs) are inevitably affected by aging. The effect of age on EpiSCs and wound healing needs to be further explored.\nMETHODS: Skin RNA-seq data of young (5 months) and old (30 months) CB6F1 mice were obtained from GEO Series GSE35322 with 10 in each age group. Differentially expressed genes were analyzed, and EpiSCs-related pathways were enriched by KEGG. The age-related changes of the screened PI3K/Akt pathway were validated by Western Blot and immunofluorescence of epidermis of SD rats (2, 17, and 23 months, n = 6). The expression of upstream protein EGFR was assessed by immunofluorescence in skin of mice (4, 13, and 23 months, n = 6) and human (respectively, 23, 28, 30 years old in the young group and 69, 73, 78 years old in the old group) skin. Inhibitors of EGFR were used to verify its effects on EpiSCs and wound healing. The small molecule drug Tideglusib was tested for its effects on signaling pathways of EpiSCs and wound healing of aged rats. Western Blot was used for the detection of signaling pathways in in vitro experiments. Cell migration assays were used to assess cell migration ability. Flow cytometry was used to detect changes in cell cycle and apoptosis levels. Sulforhodamine B assay and CCK-8 assay were used to evaluate cell proliferation and viability, respectively. Student's t test and one-way analysis of variance (ANOVA) followed by the multiple comparisons Bonferroni test were used for statistical analysis. The 0.05 level of confidence was accepted as a significant difference.\nRESULTS: EpiSCs-related PI3K/Akt pathway was enriched by KEGG and verified by decreased phosphorylation of Akt (32.1 ± 13.8%, P < 0.01) and mTOR (38.9 ± 11.8%, P < 0.01) in aged epidermis of rats. Furthermore, the expression of PI3K/Akt-upstream EGFR decreased with age in the epidermis of mouse (27.6 ± 5.5%, P < 0.01) and human (25.8 ± 9.3%, P < 0.01). With EGFR blocked by Erlotinib, EpiSCs showed reduced phosphorylation of Akt (30.4 ± 10.6%, P < 0.01) and mTOR (39.8 ± 12.8%, P < 0.01), impaired proliferation and migration after incubated for 24 h and 36 h (P < 0.05), and higher levels of apoptosis (11.9 ± 1.7%, P < 0.05), and rats showed slower wound healing from d7 to d14 after wounding (P < 0.01). In addition to slower wound healing rates, aged rats also showed a decrease in the efficacy of EGF, partly due to the downregulated EGFR expression. By activating PI3K/Akt pathway, Tideglusib promoted the proliferation and migration of EpiSCs with apoptosis inhibited (P < 0.01) and accelerated wound healing in aged rats from d7 to d14 after wounding (P < 0.05). Notably, the combined use of Tideglusib and EGF could further enhance wound healing in aged rats.\nCONCLUSIONS: The decreased expression of EGFR in epidermis with age resulted in decreased activity of the PI3K/Akt pathway and limited EGF efficacy. Tideglusib could assist wound healing in aged rats via activating PI3K/Akt pathway, which may be considered as an ingredient for medical and cosmetics use.", "claims": [{"id": "claim-method", "statement": "The statistical analysis was performed by two-tailed unpaired Student’s t test, one-way analysis of variance (ANOVA) followed by the multiple comparisons Bonferroni test and presented as the mean ± SD using the Prism software (GraphPad).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35729652", "locator": "sections[14] \"Quantification and statistical analysis\" paragraph 2", "quote": "The statistical analysis was performed by two-tailed unpaired Student’s t test, one-way analysis of variance (ANOVA) followed by the multiple comparisons Bonferroni test and presented as the mean ± SD using the Prism software (GraphPad)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Further information and requests for reagents may be directed to and will be fulfilled by the Lead Contact: Chuan’an Shen (shenchuanan@126.com).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35729652", "locator": "sections[29] \"notes\" paragraph 1", "quote": "Further information and requests for reagents may be directed to and will be fulfilled by the Lead Contact: Chuan’an Shen (shenchuanan@126.com)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:35729652"], "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. 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METHODS: Skin RNA-seq data of young (5 months) and old (30 months)"], "order_basis": "paper_text_order:342", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["f young (5 months) and old (30 months) CB6F1 mice were obtained from GEO Series GSE35322 with 10 in", "EGFR decreased with age in the epidermis of mouse (27.6 ± 5.5%, P < 0.01) and human (25.8 ± 9.", "ot and immunofluorescence of epidermis of SD rats (2, 17, and 23 months, n = 6). The expressio", "pathways of EpiSCs and wound healing of aged rats. Western Blot was used for the detection of"], "order_basis": "paper_text_order:400", "id": "assay:2"}, {"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": ["screened PI3K/Akt pathway were validated by Western Blot and immunofluorescence of epidermis of SD ra", "ys of EpiSCs and wound healing of aged rats. Western Blot was used for the detection of signaling path", "es of rats of different ages were exposed to Western Blot for detection of the PI3K/Akt pathway. After"], "order_basis": "paper_text_order:644", "id": "assay:3"}, {"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": ["t pathway were validated by Western Blot and immunofluorescence of epidermis of SD rats (2, 17, and 23 month", "ion of upstream protein EGFR was assessed by immunofluorescence in skin of mice (4, 13, and 23 months, n = 6"], "order_basis": "paper_text_order:660", "id": "assay:4"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["were used to assess cell migration ability. Flow cytometry was used to detect changes in cell cycle and"], "order_basis": "paper_text_order:1329", "id": "assay:5"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["was used to detect changes in cell cycle and apoptosis levels. Sulforhodamine B assay and CCK-8 ass", "h and 36 h (P < 0.05), and higher levels of apoptosis (11.9 ± 1.7%, P < 0.05), and rats showed slo", "e proliferation and migration of EpiSCs with apoptosis inhibited (P < 0.01) and accelerated wound h", "apoptosis levels. Sulforhodamine B assay and CCK-8 assay were used to evaluate cell proliferati"], "order_basis": "paper_text_order:1388", "id": "assay:6"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["the experiments. For experiments, cells were cultured in Epilife culture medium with or without Erlot", "d [10]. Independent clones were cultured and passaged in Epilife culture medium (MEPI500CA, Gibco)"], "order_basis": "paper_text_order:5778", "id": "assay:7"}, {"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": 1.0, "evidence": ["The statistical analysis was performed by two-tailed unpaired Student’s t test, one-way analysis of variance (ANOVA) followed by the multiple comparisons Bonferroni test and presented as the mean ± SD using the Prism software (GraphPad)."], "order_basis": "consumes_earlier_output", "id": "assay:8"}]}