{"doi":"10.3389/fphys.2020.00209","title":"EDN1-AS, A Novel Long Non-coding RNA Regulating Endothelin-1 in Human Proximal Tubule Cells","abstract":"Endothelin-1 (ET-1) is a peptide hormone that functions as a vasoconstrictor in the vasculature, whereas in the collecting duct of the kidney it exerts blood pressure-lowering effects via natriuretic actions. Aberrant ET-1 signaling is associated with several pathological states including hypertension and chronic kidney disease. ET-1 expression is regulated largely through transcriptional control of the gene that encodes ET-1, EDN1. Here we report a long, non-coding RNA (lncRNA) that appears to be antisense to the EDN1 gene, called EDN1-AS. Because EDN1-AS represents a potential novel mechanism to regulate ET-1 expression, we examined the regulation of EDN1-AS expression and action. A putative glucocorticoid receptor response (GR) element upstream of the predicted EDN1-AS transcription start site was identified using the ENCODE database and the UCSC genome browser. Two homozygous deletion clones of the element were generated using CRISPR/Cas9. This deletion resulted in a significant increase in the expression of EDN1-AS, which was associated with increased secretion of ET-1 peptide from HK-2 cells (2-fold increase in KO cells vs. CNTL, n=7, P<0.05). Phenotypic characterization of these CRISPR clones revealed a difference in cell growth rates. Using a standard growth assay, we determined that the KO1 clone exhibited a 3-fold increase in growth over 8 days compared to control cells (n=4, P<0.01) and the KO2 clone exhibited a 2-fold increase (n=4, P<0.01). These results support a role for EDN1-AS as a novel regulatory mechanism of ET-1 expression and cellular proliferation.","journal":"Frontiers in Physiology","year":2020,"id":86814,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":343664,"name":"Kristen Solocinski","orcid":null,"position":1,"is_corresponding":false},{"id":316123,"name":"Sarah Masten","orcid":null,"position":2,"is_corresponding":false},{"id":316126,"name":"Dominique Barral","orcid":null,"position":3,"is_corresponding":false},{"id":442953,"name":"Sarah J. Barilovits","orcid":null,"position":4,"is_corresponding":false},{"id":442140,"name":"Lauren A. Jeffers","orcid":"0000-0001-8602-4828","position":5,"is_corresponding":false},{"id":361074,"name":"Kareme D. Alder","orcid":"0000-0002-7796-4188","position":6,"is_corresponding":false},{"id":442954,"name":"Ravi Patel","orcid":null,"position":7,"is_corresponding":false},{"id":316129,"name":"Charles S. Wingo","orcid":null,"position":8,"is_corresponding":false},{"id":442141,"name":"Kevin D. Brown","orcid":"0000-0003-3020-8964","position":9,"is_corresponding":false},{"id":442955,"name":"Brian Cain","orcid":null,"position":10,"is_corresponding":false},{"id":314944,"name":"Michelle L. Gumz","orcid":"0000-0002-1342-0878","position":11,"is_corresponding":false},{"id":314941,"name":"Lauren G. Douma","orcid":"0000-0001-8216-9253","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T21:59:03.706190Z","pmid":"32231591","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":[]}