{"doi":"10.14814/phy2.70021","title":"<scp>miR</scp>‐495 promotes intestinal epithelial cell apoptosis through downregulation of Sphingosine‐1‐phosphate","abstract":"Many pathological conditions lead to defects in intestinal epithelial integrity and loss of barrier function; Sphingosine-1-phosphate (S1P) has been shown to augment intestinal barrier integrity, though the exact mechanisms are not completely understood. We have previously shown that overexpression of Sphingosine Kinase 1 (SphK1), the rate limiting enzyme for S1P synthesis, significantly increased S1P production and cell proliferation. Here we show that microRNA 495 (miR-495) upregulation led to decreased levels of SphK1 resultant from a direct effect at the SphK1 mRNA. Increasing expression of miR-495 in intestinal epithelial cells resulted in decreased proliferation and increased susceptibility to apoptosis. Transgenic expression of miR-495 inhibited mucosal growth, as well as decreased proliferation in the crypts. The intestinal villi also expressed decreased levels of barrier proteins and exaggerated damage upon exposure to cecal ligation-puncture. These results implicate miR-495 as a critical negative regulator of intestinal epithelial protection and proliferation through direct regulation of SphK1, the rate limiting enzyme critical for production of S1P.","journal":"Physiological Reports","year":2024,"id":481413,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"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":1237617,"name":"Cassandra A. Cairns","orcid":"0000-0002-4364-4418","position":1,"is_corresponding":false},{"id":637712,"name":"Tingxi Yu","orcid":null,"position":2,"is_corresponding":false},{"id":1321464,"name":"Rao N. Jaladanki","orcid":null,"position":3,"is_corresponding":false},{"id":691698,"name":"Claire M. Dodson","orcid":null,"position":4,"is_corresponding":false},{"id":293824,"name":"Hee Kyoung Chung","orcid":null,"position":5,"is_corresponding":false},{"id":518017,"name":"Lan Xiao","orcid":"0000-0003-1876-655X","position":6,"is_corresponding":false},{"id":292776,"name":"Jian‐Ying Wang","orcid":"0000-0003-3002-1040","position":7,"is_corresponding":false},{"id":490258,"name":"Douglas J. Turner","orcid":"0000-0002-5244-0417","position":8,"is_corresponding":false},{"id":550080,"name":"Ruiyun Li","orcid":"0000-0001-8927-9965","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":null,"created_at":"2026-07-19T02:07:06.225103Z","pmid":"39261977","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":[]}