{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:50:01Z","timestamp":1788821401121,"version":"build-2803163510"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["23am0401007"],"award-info":[{"award-number":["23am0401007"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"name":"JSPS KAKENHI","award":["JP21H05025"],"award-info":[{"award-number":["JP21H05025"]}]},{"name":"JSPS KAKENHI","award":["23H04067"],"award-info":[{"award-number":["23H04067"]}]},{"name":"Joint Research on ExCELLS","award":["24EXC207"],"award-info":[{"award-number":["24EXC207"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["23am0401007"],"award-info":[{"award-number":["23am0401007"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"name":"JSPS KAKENHI","award":["JP21H05025"],"award-info":[{"award-number":["JP21H05025"]}]},{"name":"JSPS KAKENHI","award":["23H04067"],"award-info":[{"award-number":["23H04067"]}]},{"name":"Joint Research on ExCELLS","award":["24EXC207"],"award-info":[{"award-number":["24EXC207"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Systemically administered anti\u2013microRNA (miR)-21-serinol nucleic acid (SNA) accumulates in the kidneys and suppresses renal cyst growth.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Anti\u2013miR-21-SNA treatment alters mitochondrial metabolism, apoptotic signaling, and inhibits kidney tissue fibrosis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            In human autosomal dominant polycystic kidney disease kidney cells, anti\u2013miR-21-SNA treatment reduces cyst size and intracellular cAMP content and increases Ca2\n                            <jats:sup>+<\/jats:sup>\n                            concentration.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hereditary cystic kidney diseases are ciliopathies characterized by functional defects in the primary cilia of renal tubules. Abnormalities in the primary cilia enhance cell proliferation signals and cause cyst enlargement. The most common type is autosomal dominant polycystic kidney disease (ADPKD), but other diseases, such as nephronophthisis, have been discovered to be more common than previously considered. In ADPKD, several microRNAs are reportedly aberrantly expressed and involved in disease pathogenesis. Among these, we focused on microRNA (miR)-21, which is upregulated in response to cAMP signaling. In this study, we aimed to newly generate an anti\u2013miR-21 oligonucleotide synthesized from serinol nucleic acid (anti\u2013miR-21-SNA) to improve anti-microRNA activity and investigate its effects on cyst growth\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated the effectiveness of anti\u2013miR-21 treatment using an serinol nucleic acid\u2013based antisense oligonucleotide in a mouse model of cystic kidney disease and human ADPKD cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our study revealed that anti\u2013miR-21-SNA effectively prevented cyst growth\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . In the mouse model of cystic kidney disease, we systemically administered anti\u2013miR-21-SNA and observed its accumulation primarily in the kidneys, suggesting effective drug delivery. Anti\u2013miR-21-SNA treatment reduced kidney size and blood urea nitrogen levels without inducing hepatotoxicity. Mechanistically, molecules related to mitochondrial metabolism, apoptosis, and fibrosis pathways were involved.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      , anti\u2013miR-21-SNA treatment of primary cultured kidney cells from an ADPKD patient reduced cyst volume and intracellular cAMP content and increased Ca\n                      <jats:sup>2+<\/jats:sup>\n                      concentration, supporting the efficacy of this treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results showed that anti\u2013miR-21-SNA treatment represents a potential therapeutic strategy for cystic kidney disease.<\/jats:p>\n                  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