{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T17:12:27Z","timestamp":1769188347314,"version":"3.49.0"},"reference-count":22,"publisher":"S. Karger AG","issue":"5-6","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background\/Aims:&lt;\/i&gt;&lt;\/b&gt; Both endothelin-1 (ET-1) and the renin-angiotensin system (RAS) are implicated in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). In the present study, we explored the interaction between ET-1 and the RAS by examining the effect of ET-1 on angiotensin-converting enzyme-2 (ACE2) expression and activity in human bronchial epithelial cells (HBEpCs). &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; HBEpCs were treated with ET-1 (1, 10, 20, 40 or 50 nmol\/l) for 6, 12, 18, 24 or 30 h with or without the transcription inhibitor actinomycin D, endothelin A (ETA) receptor blocker BQ123, endothelin B receptor blocker BQ788, or different kinase inhibitors. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; ET-1 decreased the ACE2 mRNA level in a dose- and time-dependent manner within 24 h, which led to dose-dependent downregulation of the ACE2 promoter activity, protein level and the cell membrane ACE2 activity. Actinomycin D (1 mg\/ml), BQ123 (1 \u03bcmol\/l), and the p38 mitogen-activated protein kinase (MAPK) siRNA and inhibitor PD169316 (25 \u03bcmol\/l) completely abolished the effect of ET-1 on ACE2 expression in HBEpCs. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; ET-1 downregulates ACE2 expression and activity at the transcription level in HBEpCs via the ETA receptor by a p38 MAPK-dependent mechanism. This is the first evidence of crosstalk between the ET-1\/ETA axis and the RAS in regard to the pathogenesis and progression of COPD.<\/jats:p>","DOI":"10.1159\/000350395","type":"journal-article","created":{"date-parts":[[2013,6,5]],"date-time":"2013-06-05T08:28:24Z","timestamp":1370420904000},"page":"297-304","source":"Crossref","is-referenced-by-count":22,"title":["Endothelin-1 Downregulates Angiotensin-Converting Enzyme-2 Expression in Human Bronchial Epithelial Cells"],"prefix":"10.1159","volume":"91","author":[{"given":"Hongliang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yamin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renrong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Ou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2013,6,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1164%2Frccm.200703-456SO"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1185%2F03007990902868971"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.2174%2F1381612033455431"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.2174%2F092986711796642562"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1002%2Femmm.201000080"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1183%2F09031936.06.00053805"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.M200581200"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.pbiomolbio.2005.05.011"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1097%2FFJC.0b013e3180986219"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038%2Fnm1267"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1007%2Fs00018-007-6228-6"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1186%2Frr44"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016%2FS0143-4179%2896%2990038-4"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1159%2F000196349"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1136%2Fthorax.56.1.30"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.peptides.2011.08.009"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.1001253107"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1359%2Fjbmr.2002.17.10.1774"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1371%2Fjournal.pone.0022806"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1042%2FCS20120081"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1365-2222.1994.tb00243.x"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.pupt.2010.12.006"}],"container-title":["Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/350395","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/350395","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T18:17:21Z","timestamp":1745432241000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000350395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013]]},"references-count":22,"journal-issue":{"issue":"5-6","published-online":{"date-parts":[[2013,7,1]]},"published-print":{"date-parts":[[2013,7,19]]}},"URL":"https:\/\/doi.org\/10.1159\/000350395","archive":["Portico"],"relation":{},"ISSN":["0031-7012","1423-0313"],"issn-type":[{"value":"0031-7012","type":"print"},{"value":"1423-0313","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013]]}}}