{"doi":"10.1016/j.ajpath.2025.11.003","title":"Loss of Angptl4 Protects Mice from Intestinal Colitis and Tumorigenesis with Alternative Activation of Macrophages","abstract":"Angiopoietin-like 4 (Angptl4) is a secreted glycoprotein involved in the regulation of various homeostatic and disease processes. In the intestine, prior studies have suggested protective roles for Angptl4 in inflammation using Angptl4 knockout mouse models; however, phenotypic variability-such as perinatal lethality and intestinal inflammation accompanied by lymphatic defects in only a subset of animals-has complicated the interpretation of its role in intestinal pathogenesis. In this study, the impact of Angptl4 deficiency was examined using a subset of Angptl4 knockout mice that survive postnatally without overt abnormalities. It was found that loss of Angptl4 confers protection against colitis and colitis-associated colorectal tumorigenesis. These protective effects were associated with the alternative activation of anti-inflammatory M2-like macrophages. Similarly, in a genetic model of intestinal tumorigenesis, Angptl4 deficiency resulted in reduced tumor burden and attenuated inflammation, accompanied by increased M2-like macrophages. Analysis of human colorectal cancer data sets further revealed that low ANGPTL4 expression is associated with improved survival outcomes as well as reduced expression of inflammation-related marker genes. Collectively, the findings uncover a previously unrecognized protective effect of Angptl4 deficiency against intestinal pathogenesis via anti-inflammatory mechanisms, suggesting Angptl4 as a potential therapeutic target and prognostic biomarker for colorectal cancer and inflammatory bowel disease.","journal":"The American Journal of Pathology","year":2025,"id":8373,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-12-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":73335,"name":"Yun Hye Kim","orcid":null,"position":1,"is_corresponding":false},{"id":73336,"name":"Min Seon Choe","orcid":"0009-0008-2239-6815","position":2,"is_corresponding":false},{"id":73337,"name":"Hamza Sghayare","orcid":"0009-0009-7145-2534","position":3,"is_corresponding":false},{"id":73338,"name":"Qiwei Zhang","orcid":"0000-0002-2770-111X","position":4,"is_corresponding":false},{"id":73339,"name":"Gaeun Kwon","orcid":null,"position":5,"is_corresponding":false},{"id":73340,"name":"Yeeun Kim","orcid":"0000-0003-2764-5709","position":6,"is_corresponding":false},{"id":73341,"name":"Seoyeon Lee","orcid":null,"position":7,"is_corresponding":false},{"id":73342,"name":"Chaewon Lee","orcid":"0000-0003-3639-5262","position":8,"is_corresponding":false},{"id":73343,"name":"Hoon-Ki Sung","orcid":null,"position":9,"is_corresponding":false},{"id":73344,"name":"Joe Eun Son","orcid":"0000-0003-3066-2796","position":10,"is_corresponding":false},{"id":73345,"name":"Gye Cheol Kwon","orcid":"0000-0002-4886-0590","position":11,"is_corresponding":false},{"id":73346,"name":"Seo-Yeon Lee","orcid":"0000-0003-0908-3749","position":12,"is_corresponding":false},{"id":73347,"name":"Hoon‐Ki Sung","orcid":"0000-0001-6677-9385","position":13,"is_corresponding":false},{"id":73334,"name":"Jeong-ah Yoo","orcid":null,"position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}