Spermidine Prevents Polarity Loss of Absorptive Enterocytes in Jejunum of Lipopolysaccharide-Challenged Mice via 4D-DIA Proteomics Analysis
Identifying effective compounds to restore the polarity of absorptive enterocytes (AEs) holds promise for mitigating the severity and duration of small intestinal disorders. Spermidine (SPD) is a natural polyamine; whether it can repair inflammation-induced loss of AE polarity remains unclear. In th...
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2025
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| _version_ | 1849927644775186432 |
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| author | Pengchao Zheng (22674589) |
| author2 | Shiyi Tian (5868122) Zhen Chen (129176) Yi Zhang (9093) Keyi Jiang (3603341) Ziyang Zha (22674592) Jue Wang (58890) Baosheng Liu (3042366) |
| author2_role | author author author author author author author |
| author_facet | Pengchao Zheng (22674589) Shiyi Tian (5868122) Zhen Chen (129176) Yi Zhang (9093) Keyi Jiang (3603341) Ziyang Zha (22674592) Jue Wang (58890) Baosheng Liu (3042366) |
| author_role | author |
| dc.creator.none.fl_str_mv | Pengchao Zheng (22674589) Shiyi Tian (5868122) Zhen Chen (129176) Yi Zhang (9093) Keyi Jiang (3603341) Ziyang Zha (22674592) Jue Wang (58890) Baosheng Liu (3042366) |
| dc.date.none.fl_str_mv | 2025-11-24T12:41:23Z |
| dc.identifier.none.fl_str_mv | 10.1021/acs.jproteome.5c00531.s002 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/dataset/Spermidine_Prevents_Polarity_Loss_of_Absorptive_Enterocytes_in_Jejunum_of_Lipopolysaccharide-Challenged_Mice_via_4D-DIA_Proteomics_Analysis/30694594 |
| dc.rights.none.fl_str_mv | CC BY-NC 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biochemistry Physiology Immunology Astronomical and Space Sciences not elsewhere classified Chemical Sciences not elsewhere classified small intestinal disorders proteomic analysis revealed apical slc transporters 2 cell model specific immune responses spd supplementation enhanced spd effectively alleviates spd attenuated mucosal inflammatory responses treated mice significantly downregulating results demonstrated proteins involved protein groups pards ), natural polyamine inflammatory effect induced loss independent acquisition holds promise hdac4 signaling findings indicate epithelial morphology cytoskeletal proteins crypt ratio challenged mice antioxidant capacity absorptive enterocytes 4d data |
| dc.title.none.fl_str_mv | Spermidine Prevents Polarity Loss of Absorptive Enterocytes in Jejunum of Lipopolysaccharide-Challenged Mice via 4D-DIA Proteomics Analysis |
| dc.type.none.fl_str_mv | Dataset info:eu-repo/semantics/publishedVersion dataset |
| description | Identifying effective compounds to restore the polarity of absorptive enterocytes (AEs) holds promise for mitigating the severity and duration of small intestinal disorders. Spermidine (SPD) is a natural polyamine; whether it can repair inflammation-induced loss of AE polarity remains unclear. In this study, we employed lipopolysaccharide (LPS)-challenged mice models combined with 4D data-independent acquisition (DIA) proteomics to investigate the mechanisms by which SPD alleviates polarity loss in AEs. Our results demonstrated that SPD supplementation enhanced the antioxidant capacity and improved the villus/crypt ratio in the jejunum of LPS-treated mice. Proteomic analysis revealed that LPS induced acute phase and inflammatory responses, significantly downregulating the expression of cytoskeletal proteins (Pdlim3, Pdlim7) essential for epithelial morphology as well as proteins involved in apical–basal polarity (Pard6b, Pard3, Prkcz, LLGL2), apical membrane integrity (Vil1, Pdims, Akp3, Tjps, Pards), and apical SLC transporters. Conversely, SPD attenuated mucosal- and tissue-specific immune responses and reversed the downregulation of these protein groups. Furthermore, using a Caco-2 cell model, we confirmed the anti-inflammatory effect of SPD and elucidated its role in suppressing AE polarity loss via the regulation of HDAC4 signaling. These findings indicate that SPD effectively alleviates the inflammation-induced loss of AE polarity in the jejunum of LPS-challenged mice. |
| eu_rights_str_mv | openAccess |
| id | Manara_721f81b3c6b0b2474c010e05174249df |
| identifier_str_mv | 10.1021/acs.jproteome.5c00531.s002 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30694594 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY-NC 4.0 |
| spelling | Spermidine Prevents Polarity Loss of Absorptive Enterocytes in Jejunum of Lipopolysaccharide-Challenged Mice via 4D-DIA Proteomics AnalysisPengchao Zheng (22674589)Shiyi Tian (5868122)Zhen Chen (129176)Yi Zhang (9093)Keyi Jiang (3603341)Ziyang Zha (22674592)Jue Wang (58890)Baosheng Liu (3042366)BiochemistryPhysiologyImmunologyAstronomical and Space Sciences not elsewhere classifiedChemical Sciences not elsewhere classifiedsmall intestinal disordersproteomic analysis revealedapical slc transporters2 cell modelspecific immune responsesspd supplementation enhancedspd effectively alleviatesspd attenuated mucosalinflammatory responsestreated micesignificantly downregulatingresults demonstratedproteins involvedprotein groupspards ),natural polyamineinflammatory effectinduced lossindependent acquisitionholds promisehdac4 signalingfindings indicateepithelial morphologycytoskeletal proteinscrypt ratiochallenged miceantioxidant capacityabsorptive enterocytes4d dataIdentifying effective compounds to restore the polarity of absorptive enterocytes (AEs) holds promise for mitigating the severity and duration of small intestinal disorders. Spermidine (SPD) is a natural polyamine; whether it can repair inflammation-induced loss of AE polarity remains unclear. In this study, we employed lipopolysaccharide (LPS)-challenged mice models combined with 4D data-independent acquisition (DIA) proteomics to investigate the mechanisms by which SPD alleviates polarity loss in AEs. Our results demonstrated that SPD supplementation enhanced the antioxidant capacity and improved the villus/crypt ratio in the jejunum of LPS-treated mice. Proteomic analysis revealed that LPS induced acute phase and inflammatory responses, significantly downregulating the expression of cytoskeletal proteins (Pdlim3, Pdlim7) essential for epithelial morphology as well as proteins involved in apical–basal polarity (Pard6b, Pard3, Prkcz, LLGL2), apical membrane integrity (Vil1, Pdims, Akp3, Tjps, Pards), and apical SLC transporters. Conversely, SPD attenuated mucosal- and tissue-specific immune responses and reversed the downregulation of these protein groups. Furthermore, using a Caco-2 cell model, we confirmed the anti-inflammatory effect of SPD and elucidated its role in suppressing AE polarity loss via the regulation of HDAC4 signaling. These findings indicate that SPD effectively alleviates the inflammation-induced loss of AE polarity in the jejunum of LPS-challenged mice.2025-11-24T12:41:23ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.1021/acs.jproteome.5c00531.s002https://figshare.com/articles/dataset/Spermidine_Prevents_Polarity_Loss_of_Absorptive_Enterocytes_in_Jejunum_of_Lipopolysaccharide-Challenged_Mice_via_4D-DIA_Proteomics_Analysis/30694594CC BY-NC 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/306945942025-11-24T12:41:23Z |
| spellingShingle | Spermidine Prevents Polarity Loss of Absorptive Enterocytes in Jejunum of Lipopolysaccharide-Challenged Mice via 4D-DIA Proteomics Analysis Pengchao Zheng (22674589) Biochemistry Physiology Immunology Astronomical and Space Sciences not elsewhere classified Chemical Sciences not elsewhere classified small intestinal disorders proteomic analysis revealed apical slc transporters 2 cell model specific immune responses spd supplementation enhanced spd effectively alleviates spd attenuated mucosal inflammatory responses treated mice significantly downregulating results demonstrated proteins involved protein groups pards ), natural polyamine inflammatory effect induced loss independent acquisition holds promise hdac4 signaling findings indicate epithelial morphology cytoskeletal proteins crypt ratio challenged mice antioxidant capacity absorptive enterocytes 4d data |
| status_str | publishedVersion |
| title | Spermidine Prevents Polarity Loss of Absorptive Enterocytes in Jejunum of Lipopolysaccharide-Challenged Mice via 4D-DIA Proteomics Analysis |
| title_full | Spermidine Prevents Polarity Loss of Absorptive Enterocytes in Jejunum of Lipopolysaccharide-Challenged Mice via 4D-DIA Proteomics Analysis |
| title_fullStr | Spermidine Prevents Polarity Loss of Absorptive Enterocytes in Jejunum of Lipopolysaccharide-Challenged Mice via 4D-DIA Proteomics Analysis |
| title_full_unstemmed | Spermidine Prevents Polarity Loss of Absorptive Enterocytes in Jejunum of Lipopolysaccharide-Challenged Mice via 4D-DIA Proteomics Analysis |
| title_short | Spermidine Prevents Polarity Loss of Absorptive Enterocytes in Jejunum of Lipopolysaccharide-Challenged Mice via 4D-DIA Proteomics Analysis |
| title_sort | Spermidine Prevents Polarity Loss of Absorptive Enterocytes in Jejunum of Lipopolysaccharide-Challenged Mice via 4D-DIA Proteomics Analysis |
| topic | Biochemistry Physiology Immunology Astronomical and Space Sciences not elsewhere classified Chemical Sciences not elsewhere classified small intestinal disorders proteomic analysis revealed apical slc transporters 2 cell model specific immune responses spd supplementation enhanced spd effectively alleviates spd attenuated mucosal inflammatory responses treated mice significantly downregulating results demonstrated proteins involved protein groups pards ), natural polyamine inflammatory effect induced loss independent acquisition holds promise hdac4 signaling findings indicate epithelial morphology cytoskeletal proteins crypt ratio challenged mice antioxidant capacity absorptive enterocytes 4d data |