Supplementary file 2_Resveratrol attenuates pulmonary fibrosis by inhibiting alveolar epithelial senescence via targeting SASP-related proteins: an integrated bioinformatics-experimental study.xlsx
Background<p>Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease with limited treatment options. Premature senescence of alveolar epithelial type II cells (AT2 cells) plays a critical role in PF pathogenesis. This study aimed to identify natural compounds targeting sen...
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| Бусад зохиолчид: | , , , , , , , , |
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2025
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| Нөхцлүүд: | |
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Шошго нэмэх
Шошго байхгүй, Энэхүү баримтыг шошголох эхний хүн болох!
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| _version_ | 1849927622570541056 |
|---|---|
| author | Biao Zuo (1529497) |
| author2 | Su Yuan (9516815) Chen Luo (302288) Xu-Qin Du (11434573) Yong-Can Wu (22687517) Li-Peng Shi (11434576) Jin-Xin Chen (8430351) Bo-Tao Chen (1978582) Jie Zhou (28945) Yi Ren (30049) |
| author2_role | author author author author author author author author author |
| author_facet | Biao Zuo (1529497) Su Yuan (9516815) Chen Luo (302288) Xu-Qin Du (11434573) Yong-Can Wu (22687517) Li-Peng Shi (11434576) Jin-Xin Chen (8430351) Bo-Tao Chen (1978582) Jie Zhou (28945) Yi Ren (30049) |
| author_role | author |
| dc.creator.none.fl_str_mv | Biao Zuo (1529497) Su Yuan (9516815) Chen Luo (302288) Xu-Qin Du (11434573) Yong-Can Wu (22687517) Li-Peng Shi (11434576) Jin-Xin Chen (8430351) Bo-Tao Chen (1978582) Jie Zhou (28945) Yi Ren (30049) |
| dc.date.none.fl_str_mv | 2025-11-26T06:34:34Z |
| dc.identifier.none.fl_str_mv | 10.3389/fphar.2025.1680998.s002 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/dataset/Supplementary_file_2_Resveratrol_attenuates_pulmonary_fibrosis_by_inhibiting_alveolar_epithelial_senescence_via_targeting_SASP-related_proteins_an_integrated_bioinformatics-experimental_study_xlsx/30718910 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Pharmacology bleomycin-induced pulmonary fibrosis in mice resveratrol alveolar epithelial senescence bioinformatics senescence-associated secretory phenotype(SASP) |
| dc.title.none.fl_str_mv | Supplementary file 2_Resveratrol attenuates pulmonary fibrosis by inhibiting alveolar epithelial senescence via targeting SASP-related proteins: an integrated bioinformatics-experimental study.xlsx |
| dc.type.none.fl_str_mv | Dataset info:eu-repo/semantics/publishedVersion dataset |
| description | Background<p>Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease with limited treatment options. Premature senescence of alveolar epithelial type II cells (AT2 cells) plays a critical role in PF pathogenesis. This study aimed to identify natural compounds targeting senescence-related pathways for PF treatment.</p>Methods<p>An integrated approach was implemented, combining bioinformatics, artificial intelligence (AI)-assisted molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling, and experimental validation. Core targets associated with aging-related pulmonary fibrosis (PF) were identified via database mining (GeneCards and AgingAtlas) and protein-protein interaction (PPI) network analysis. Natural compounds were screened using the HERB database, and resveratrol (RES) was selected due to its multi-target activity and favorable ADMET characteristics. The efficacy of RES was evaluated through in vitro experiments using bleomycin (BLM)-induced senescent A549 alveolar epithelial cells and in vivo studies in a BLM-induced PF mouse model (C57BL/6J). Molecular docking simulations were performed to predict the binding affinity between RES and key targets, including SERPINE1, MMP2, and IL-6.</p>Results<p>Bioinformatics identified 322 aging-related PF targets, with TP53, AKT1, STAT3, JUN, and NFKB1 as core regulators. Resveratrol was selected as a top candidate modulating all five core targets and exhibiting optimal drug-likeness. Molecular docking and dynamics simulations confirmed strong binding affinity between RES and key senescence-associated proteins (SERPINE1: −8 kcal/mol; MMP2: −7.5 kcal/mol; IL-6: −7.1 kcal/mol). In vitro, RES (10–40 μM) significantly suppressed bleomycin-induced senescence in A549 cells, reducing SA-β-Gal activity and downregulating SERPINE1, MMP2, and IL6 expression. In vivo, RES treatment (20–80 mg/kg, 21 days) attenuated bleomycin-induced PF in mice, improving weight loss, reducing alveolar damage, inflammation, and collagen deposition (Masson’s trichrome) in a dose-dependent manner.</p>Conclusion<p>Resveratrol effectively inhibits alveolar epithelial cell senescence and ameliorates pulmonary fibrosis, likely by targeting key senescence-associated pathways (e.g., SERPINE1, MMP2, IL-6). This study provides a promising transdisciplinary strategy for anti-fibrotic drug discovery and highlights RES as a potential therapeutic candidate for PF.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_24ebd566d0807808c17dfba01749caa6 |
| identifier_str_mv | 10.3389/fphar.2025.1680998.s002 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30718910 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Supplementary file 2_Resveratrol attenuates pulmonary fibrosis by inhibiting alveolar epithelial senescence via targeting SASP-related proteins: an integrated bioinformatics-experimental study.xlsxBiao Zuo (1529497)Su Yuan (9516815)Chen Luo (302288)Xu-Qin Du (11434573)Yong-Can Wu (22687517)Li-Peng Shi (11434576)Jin-Xin Chen (8430351)Bo-Tao Chen (1978582)Jie Zhou (28945)Yi Ren (30049)Pharmacologybleomycin-induced pulmonary fibrosis in miceresveratrolalveolar epithelial senescencebioinformaticssenescence-associated secretory phenotype(SASP)Background<p>Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease with limited treatment options. Premature senescence of alveolar epithelial type II cells (AT2 cells) plays a critical role in PF pathogenesis. This study aimed to identify natural compounds targeting senescence-related pathways for PF treatment.</p>Methods<p>An integrated approach was implemented, combining bioinformatics, artificial intelligence (AI)-assisted molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling, and experimental validation. Core targets associated with aging-related pulmonary fibrosis (PF) were identified via database mining (GeneCards and AgingAtlas) and protein-protein interaction (PPI) network analysis. Natural compounds were screened using the HERB database, and resveratrol (RES) was selected due to its multi-target activity and favorable ADMET characteristics. The efficacy of RES was evaluated through in vitro experiments using bleomycin (BLM)-induced senescent A549 alveolar epithelial cells and in vivo studies in a BLM-induced PF mouse model (C57BL/6J). Molecular docking simulations were performed to predict the binding affinity between RES and key targets, including SERPINE1, MMP2, and IL-6.</p>Results<p>Bioinformatics identified 322 aging-related PF targets, with TP53, AKT1, STAT3, JUN, and NFKB1 as core regulators. Resveratrol was selected as a top candidate modulating all five core targets and exhibiting optimal drug-likeness. Molecular docking and dynamics simulations confirmed strong binding affinity between RES and key senescence-associated proteins (SERPINE1: −8 kcal/mol; MMP2: −7.5 kcal/mol; IL-6: −7.1 kcal/mol). In vitro, RES (10–40 μM) significantly suppressed bleomycin-induced senescence in A549 cells, reducing SA-β-Gal activity and downregulating SERPINE1, MMP2, and IL6 expression. In vivo, RES treatment (20–80 mg/kg, 21 days) attenuated bleomycin-induced PF in mice, improving weight loss, reducing alveolar damage, inflammation, and collagen deposition (Masson’s trichrome) in a dose-dependent manner.</p>Conclusion<p>Resveratrol effectively inhibits alveolar epithelial cell senescence and ameliorates pulmonary fibrosis, likely by targeting key senescence-associated pathways (e.g., SERPINE1, MMP2, IL-6). This study provides a promising transdisciplinary strategy for anti-fibrotic drug discovery and highlights RES as a potential therapeutic candidate for PF.</p>2025-11-26T06:34:34ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.3389/fphar.2025.1680998.s002https://figshare.com/articles/dataset/Supplementary_file_2_Resveratrol_attenuates_pulmonary_fibrosis_by_inhibiting_alveolar_epithelial_senescence_via_targeting_SASP-related_proteins_an_integrated_bioinformatics-experimental_study_xlsx/30718910CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307189102025-11-26T06:34:34Z |
| spellingShingle | Supplementary file 2_Resveratrol attenuates pulmonary fibrosis by inhibiting alveolar epithelial senescence via targeting SASP-related proteins: an integrated bioinformatics-experimental study.xlsx Biao Zuo (1529497) Pharmacology bleomycin-induced pulmonary fibrosis in mice resveratrol alveolar epithelial senescence bioinformatics senescence-associated secretory phenotype(SASP) |
| status_str | publishedVersion |
| title | Supplementary file 2_Resveratrol attenuates pulmonary fibrosis by inhibiting alveolar epithelial senescence via targeting SASP-related proteins: an integrated bioinformatics-experimental study.xlsx |
| title_full | Supplementary file 2_Resveratrol attenuates pulmonary fibrosis by inhibiting alveolar epithelial senescence via targeting SASP-related proteins: an integrated bioinformatics-experimental study.xlsx |
| title_fullStr | Supplementary file 2_Resveratrol attenuates pulmonary fibrosis by inhibiting alveolar epithelial senescence via targeting SASP-related proteins: an integrated bioinformatics-experimental study.xlsx |
| title_full_unstemmed | Supplementary file 2_Resveratrol attenuates pulmonary fibrosis by inhibiting alveolar epithelial senescence via targeting SASP-related proteins: an integrated bioinformatics-experimental study.xlsx |
| title_short | Supplementary file 2_Resveratrol attenuates pulmonary fibrosis by inhibiting alveolar epithelial senescence via targeting SASP-related proteins: an integrated bioinformatics-experimental study.xlsx |
| title_sort | Supplementary file 2_Resveratrol attenuates pulmonary fibrosis by inhibiting alveolar epithelial senescence via targeting SASP-related proteins: an integrated bioinformatics-experimental study.xlsx |
| topic | Pharmacology bleomycin-induced pulmonary fibrosis in mice resveratrol alveolar epithelial senescence bioinformatics senescence-associated secretory phenotype(SASP) |