{"doi":"10.3390/antiox13091067","title":"Cystathionine Gamma-Lyase Regulates TNF-α-Mediated Injury Response in Human Colonic Epithelial Cells and Colonoids","abstract":"Cystathionine gamma-lyase (CSE) and TNF-α are now recognized as key regulators of intestinal homeostasis, inflammation, and wound healing. In colonic epithelial cells, both molecules have been shown to influence a variety of biological processes, but the specific interactions between intracellular signaling pathways regulated by CSE and TNF-α are poorly understood. In the present study, we investigated these interactions in normal colonocytes and an organoid model of the healthy human colon using CSE-specific pharmacological inhibitors and siRNA-mediated transient gene silencing in analytical and functional assays in vitro. We demonstrated that CSE and TNF-α mutually regulated each other’s functions in colonic epithelial cells. TNF-α treatment stimulated CSE activity within minutes and upregulated CSE expression after 24 h, increasing endogenous CSE-derived H2S production. In turn, CSE activity promoted TNF-α-induced NF-ĸB and ERK1/2 activation but did not affect the p38 MAPK signaling pathway. Inhibition of CSE activity completely abolished the TNF-α-induced increase in transepithelial permeability and wound healing. Our data suggest that CSE activity may be essential for effective TNF-α-mediated intestinal injury response. Furthermore, CSE regulation of TNF-α-controlled intracellular signaling pathways could provide new therapeutic targets in diseases of the colon associated with impaired epithelial wound healing.","journal":"Antioxidants","year":2024,"id":477455,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":919163,"name":"Gábor Törő","orcid":null,"position":1,"is_corresponding":false},{"id":1315740,"name":"Peter Szaniszlo","orcid":"0000-0002-3565-0957","position":2,"is_corresponding":false},{"id":913105,"name":"Manjit Maskey","orcid":"0000-0003-2461-1538","position":3,"is_corresponding":false},{"id":913774,"name":"Ketan Thanki","orcid":null,"position":4,"is_corresponding":false},{"id":530998,"name":"Walter A. Koltun","orcid":null,"position":5,"is_corresponding":false},{"id":782688,"name":"Gregory S. Yochum","orcid":"0000-0002-1211-3040","position":6,"is_corresponding":false},{"id":354553,"name":"Irina V. Pinchuk","orcid":null,"position":7,"is_corresponding":false},{"id":913779,"name":"Celia Chao","orcid":null,"position":8,"is_corresponding":false},{"id":913780,"name":"Mark R. Hellmich","orcid":null,"position":9,"is_corresponding":false},{"id":452591,"name":"Katalin Módis","orcid":"0000-0002-0706-9196","position":10,"is_corresponding":false},{"id":913777,"name":"Francisco Arroyo Almenas","orcid":null,"position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:06:37.812633Z","pmid":"39334726","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":[]}