دورية أكاديمية
EDN1-AS , A Novel Long Non-coding RNA Regulating Endothelin-1 in Human Proximal Tubule Cells.
العنوان: | EDN1-AS , A Novel Long Non-coding RNA Regulating Endothelin-1 in Human Proximal Tubule Cells. |
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المؤلفون: | Douma LG; Department of Medicine, University of Florida, Gainesville, FL, United States.; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States., Solocinski K; Department of Medicine, University of Florida, Gainesville, FL, United States., Masten SH; Department of Medicine, University of Florida, Gainesville, FL, United States., Barral DH; Department of Medicine, University of Florida, Gainesville, FL, United States., Barilovits SJ; Department of Medicine, University of Florida, Gainesville, FL, United States., Jeffers LA; Department of Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, GA, United States., Alder KD; Yale University School of Medicine, New Haven, CT, United States., Patel R; Department of Medicine, University of Florida, Gainesville, FL, United States., Wingo CS; Department of Medicine, University of Florida, Gainesville, FL, United States., Brown KD; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States., Cain BD; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States., Gumz ML; Department of Medicine, University of Florida, Gainesville, FL, United States.; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States. |
المصدر: | Frontiers in physiology [Front Physiol] 2020 Mar 13; Vol. 11, pp. 209. Date of Electronic Publication: 2020 Mar 13 (Print Publication: 2020). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101549006 Publication Model: eCollection Cited Medium: Print ISSN: 1664-042X (Print) Linking ISSN: 1664042X NLM ISO Abbreviation: Front Physiol Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Research Foundation |
مستخلص: | 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 (two-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 three-fold increase in growth over 8 days compared to control cells ( n = 4, P < 0.01) and the KO2 clone exhibited a two-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. (Copyright © 2020 Douma, Solocinski, Masten, Barral, Barilovits, Jeffers, Alder, Patel, Wingo, Brown, Cain and Gumz.) |
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معلومات مُعتمدة: | P30 AG028740 United States AG NIA NIH HHS; R01 DK109570 United States DK NIDDK NIH HHS; R21 AG052861 United States AG NIA NIH HHS; T32 GM008169 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: CRISPR; circadian rhythm; kidney; long non-coding RNA; proximal tubule cells |
تواريخ الأحداث: | Date Created: 20200402 Latest Revision: 20210129 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC7082230 |
DOI: | 10.3389/fphys.2020.00209 |
PMID: | 32231591 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1664-042X |
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DOI: | 10.3389/fphys.2020.00209 |