{"doi":"10.1101/2022.03.03.482713","title":"Endothelial FOXC1 and FOXC2 promote intestinal regeneration after ischemia-reperfusion injury","abstract":"Abstract Intestinal ischemia induces mucosal damage while simultaneously activating intestinal stem cells (ISCs), which subsequently regenerate the damaged intestinal epithelium. However, whether paracrine factors secreted from vascular endothelial cells (ECs) - blood and lymphatic ECs (BECs and LECs, respectively) – regulate ISC-mediated regeneration have yet to be elucidated. Here, we identify FOXC1 and FOXC2 as essential regulators of paracrine signaling in regeneration of the small intestine after ischemia-reperfusion (I/R) injury. EC- and LEC-specific deletions of Foxc1 , Foxc2 , or both in mice augment I/R-induced intestinal damage by causing defects in vascular regrowth, expression of the chemokine CXCL12 and the Wnt activator R- spondin 3 in BECs and LECs, respectively, and activation of Wnt signaling in ISCs. Treatment with CXCL12 and R-spondin 3 rescues the I/R-induced intestinal damage in EC- and LEC- Foxc mutant mice, respectively. This study provides evidence that FOXC1 and FOXC2 are required for intestinal regeneration by stimulating paracrine CXCL12 and Wnt signaling.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299069,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":312365,"name":"Pieter R. Norden","orcid":"0000-0002-5960-5245","position":1,"is_corresponding":false},{"id":6248,"name":"Ting Liu","orcid":"0000-0003-1816-5551","position":2,"is_corresponding":false},{"id":940380,"name":"Naoto Ujiie","orcid":"0000-0001-9431-0912","position":3,"is_corresponding":false},{"id":826967,"name":"Xiaocai Yan","orcid":"0000-0002-9796-0504","position":4,"is_corresponding":false},{"id":988528,"name":"Kazushi Aoto","orcid":"0000-0002-0304-9622","position":5,"is_corresponding":false},{"id":284564,"name":"Sagrario Ortega","orcid":"0000-0002-1865-7102","position":6,"is_corresponding":false},{"id":505022,"name":"Isabelle G. De Plaen","orcid":"0000-0002-1742-2926","position":7,"is_corresponding":false},{"id":312371,"name":"Tsutomu Kume","orcid":"0000-0002-6005-5316","position":8,"is_corresponding":false},{"id":988527,"name":"Can Tan","orcid":"0000-0002-1450-8396","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T00:31:40.528568Z","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":[]}