{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:04:38Z","timestamp":1774591478807,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":84,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["17\/0005668"],"award-info":[{"award-number":["17\/0005668"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["16\/0005489"],"award-info":[{"award-number":["16\/0005489"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","award":["No. 115974"],"award-info":[{"award-number":["No. 115974"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022690","name":"JDRF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022690","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    In recent years, the importance of alternative splicing (AS) of certain genes in the nature and progression of diabetic nephropathy (DN) has been studied. We report a novel AS event observed in the diabetic kidney\u2014AS of the apoptosis gene\n                    <jats:italic>BCL-X<\/jats:italic>\n                    to increase the proapoptotic\n                    <jats:italic>BCL-XS<\/jats:italic>\n                    and decrease the antiapoptotic\n                    <jats:italic>BCL-XL<\/jats:italic>\n                    . This study is aimed at further investigating the role of this novel AS event in the pathogenesis of DN. To characterize important splicing events in progression of DN, human glomerular endothelial cells (GEnCs) were exposed to a diabetic environment for 1 week, and RNAseq was performed. Although several splicing events were discovered, we focused on the apoptosis gene\n                    <jats:italic>BCL-X<\/jats:italic>\n                    in the present study. In GEnCs, an upregulation of the\n                    <jats:italic>BCL-XS\/BCL-XL<\/jats:italic>\n                    ratio was observed, resulting in an increase in GEnC apoptosis. An upregulation of\n                    <jats:italic>IL-6<\/jats:italic>\n                    was also observed, and treatment with IL\u20106 alone induced a dose\u2010dependent shift in\n                    <jats:italic>BCL-X<\/jats:italic>\n                    splicing to promote expression of the proapoptotic\n                    <jats:italic>BCL-XS<\/jats:italic>\n                    . Furthermore, we identified certain splicing factors, SF3B1 and PTBP1, involved in\n                    <jats:italic>BCL-X<\/jats:italic>\n                    splicing regulation. Overexpression of the antiapoptotic\n                    <jats:italic>BCL-XL<\/jats:italic>\n                    isoform rescued apoptosis, suggesting a possible therapeutic avenue. In patients, an increase in the proapoptotic\n                    <jats:italic>BCL-XS<\/jats:italic>\n                    in urinary RNA correlated with a decline in the glomerular filtration rate, whereas in blood it correlated with the level of albuminuria. There is an increase in the proapoptotic\n                    <jats:italic>BCL-XS<\/jats:italic>\n                    isoform in the diabetic glomerular endothelium, resulting in increased GEnC apoptosis. Increased\n                    <jats:italic>BCL-XS<\/jats:italic>\n                    expression correlates with markers of renal function decline, implicating this AS event as a potential biomarker for DN severity. Furthermore, a switch of isoforms from\n                    <jats:italic>BCL-XS<\/jats:italic>\n                    to\n                    <jats:italic>BCL-XL<\/jats:italic>\n                    is highlighted as a novel therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1155\/jdr\/2840106","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T04:31:58Z","timestamp":1774585918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Splice Isoforms of the Apoptosis Gene\n                    <i>BCL-X<\/i>\n                    Have Opposing Effects in Diabetic Kidney Disease: Potential Treatment Target and Prognostic Value"],"prefix":"10.1155","volume":"2026","author":[{"given":"Megan","family":"Stevens","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica L.","family":"Ayine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Gooding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Shore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Marqueti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7890-8439","authenticated-orcid":false,"given":"Sebastian","family":"Oltean","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2016.07.002"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.37765\/ajmc.2021.88660"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.05.012"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/medicina60111821"},{"key":"e_1_2_11_5_2","first-page":"341","article-title":"Managing Hypertension Using Combination Therapy","volume":"101","author":"Smith D. 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