{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T07:20:05Z","timestamp":1779261605157,"version":"3.51.4"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,2,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Recent studies have highlighted a critical role for a group of natriuretic hormones, cardiotonic steroid (\n              <jats:styled-content style=\"fixed-case\">CTS<\/jats:styled-content>\n              ), in mediating renal inflammation and fibrosis associated with volume expanded settings, such as chronic kidney disease. Immune cell adhesion is a critical step in the inflammatory response; however, little is currently understood about the potential regulatory role of\n              <jats:styled-content style=\"fixed-case\">CTS<\/jats:styled-content>\n              signaling in this setting. Herein, we tested the hypothesis that\n              <jats:styled-content style=\"fixed-case\">CTS<\/jats:styled-content>\n              signaling through Na\n              <jats:sup>+<\/jats:sup>\n              \/K\n              <jats:sup>+<\/jats:sup>\n              \u2010\n              <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\n              ase \u03b1\u20101 (\n              <jats:styled-content style=\"fixed-case\">NKA<\/jats:styled-content>\n              \u03b1\u20101) enhances immune cell recruitment and adhesion to renal epithelium that ultimately advance renal inflammation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We demonstrate that knockdown of the \u03b1\u20101 isoform of Na\/K\u2010\n              <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\n              ase causes a reduction in\n              <jats:styled-content style=\"fixed-case\">CTS<\/jats:styled-content>\n              \u2010induced macrophage infiltration in renal tissue as well reduces the accumulation of immune cells in the peritoneal cavity in\u00a0vivo. Next, using functional adhesion assay, we demonstrate that\n              <jats:styled-content style=\"fixed-case\">CTS\u2010<\/jats:styled-content>\n              induced increases in the adhesion of macrophages to renal epithelial cells were significantly diminished after reduction of\n              <jats:styled-content style=\"fixed-case\">NKA<\/jats:styled-content>\n              \u03b1\u20101 in either macrophages or renal epithelial cells as well after inhibition of\n              <jats:styled-content style=\"fixed-case\">NKA<\/jats:styled-content>\n              \u03b1\u20101\u2010Src signaling cascade with a specific peptide inhibitor,\n              <jats:styled-content style=\"fixed-case\">pNaK<\/jats:styled-content>\n              tide in\u00a0vitro. Finally,\n              <jats:styled-content style=\"fixed-case\">CTS\u2010<\/jats:styled-content>\n              induced expression of adhesion markers in both endothelial and immune cells was significantly inhibited in an\n              <jats:styled-content style=\"fixed-case\">NKA<\/jats:styled-content>\n              \u03b1\u20101\u2010Src signaling dependent manner in\u00a0vitro.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              These findings suggest that\n              <jats:styled-content style=\"fixed-case\">CTS<\/jats:styled-content>\n              potentiates immune cell migration and adhesion to renal epithelium through an\n              <jats:styled-content style=\"fixed-case\">NKA<\/jats:styled-content>\n              \u03b1\u20101\u2013dependent mechanism; our new findings suggest that pharmacological inhibition of this feed\u2010forward loop may be useful in the treatment of renal inflammation associated with renal disease.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.013933","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T10:00:30Z","timestamp":1580378430000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Epithelial and Endothelial Adhesion of Immune Cells Is Enhanced by Cardiotonic Steroid Signaling Through Na\n            <sup>+<\/sup>\n            \/K\n            <sup>+<\/sup>\n            \u2010ATPase\u2010\u03b1\u20101"],"prefix":"10.1161","volume":"9","author":[{"given":"Fatimah K.","family":"Khalaf","sequence":"first","affiliation":[{"name":"University of Toledo College of Medicine and Life Sciences Toledo OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iman","family":"Tassavvor","sequence":"additional","affiliation":[{"name":"University of Toledo College of Medicine and Life Sciences Toledo OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amal","family":"Mohamed","sequence":"additional","affiliation":[{"name":"University of Toledo College of Medicine and Life Sciences Toledo OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Blood Research Institute Blood Center of Wisconsin Milwaukee WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak","family":"Malhotra","sequence":"additional","affiliation":[{"name":"University of Toledo College of Medicine and Life Sciences Toledo OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijian","family":"Xie","sequence":"additional","affiliation":[{"name":"Marshall Institute for Interdisciplinary Research Marshall University Huntington WV"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Tian","sequence":"additional","affiliation":[{"name":"University of Toledo College of Medicine and Life Sciences Toledo OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven T.","family":"Haller","sequence":"additional","affiliation":[{"name":"University of Toledo College of Medicine and Life Sciences Toledo OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Westfall","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences Lerner Research Institute Cleveland Clinic Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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Wilson","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences Lerner Research Institute Cleveland Clinic Cleveland OH"},{"name":"Center for Cardiovascular Diagnostics and Prevention Lerner Research Institute Cleveland Clinic Cleveland OH"},{"name":"Department of Cardiovascular Medicine, Heart and Vascular Institute Cleveland Clinic Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"University of Toledo College of Medicine and Life Sciences Toledo OH"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.13121215"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2005.11.012"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00109.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(93)90209-4"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.136.suppl_1.17625"},{"key":"e_1_3_2_7_2","first-page":"859","article-title":"Cardiotonic steroid signaling through Na\/K\u2010atpase\u2010A\u20101 and SRC kinase enhance functional interactions between immune cells and endo\/epithelial cells","volume":"66","author":"Khalaf FK","year":"2018","unstructured":"Khalaf FK, Mohamed A, Kleinhenz A, Crawford E, Tian J, Xie Z, Malhotra D, Haller S, Kennedy D. 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