{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T23:26:06Z","timestamp":1785367566922,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"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\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515140041"],"award-info":[{"award-number":["2022A1515140041"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515012036"],"award-info":[{"award-number":["2024A1515012036"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate the therapeutic potential of GSK8612, a selective TBK1 inhibitor, against the inflammatory and fibrotic pathological remodeling in the heart and kidneys induced by DOCA\/salt hypertension in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A salt\u2010sensitive hypertension model was established in male C57BL\/6 mice via uninephrectomy followed by DOCA\/salt treatment. Hypertensive mice were administered the selective TBK1 inhibitor GSK8612 (1.5 mg\/kg, i.p., once every two days) or vehicle for 21\u2009days. Blood pressure was monitored weekly. Renal and cardiac injury were assessed by histopathology, including Hematoxylin and Eosin, Sirius Red, and Masson's trichrome staining. Extracellular matrix deposition was evaluated via Western blot and immunofluorescence. Macrophage\u2010to\u2010myofibroblast transition was determined by F4\/80 and \u03b1\u2010SMA co\u2010staining. Inflammatory cell infiltration was evaluated by immunohistochemistry, while cytokine mRNA levels were quantified by RT\u2010qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      While GSK8612 treatment showed no significant effect on blood pressure in DOCA\/salt\u2010challenged mice, it significantly improved kidney function and attenuated kidney injury compared to DOCA\/salt\u2010treated controls. GSK8612 treatment significantly inhibited myofibroblast accumulation and extracellular matrix deposition in the kidneys and reduced infiltration of inflammatory cells. Furthermore, it effectively inhibited macrophage\u2010to\u2010myofibroblast transition in hypertensive nephropathy. Notably, GSK8612 administration also ameliorated DOCA\/salt\u2010induced cardiac inflammation and fibrosis, as evidenced by reduced infiltration of F4\/80\n                      <jats:sup>+<\/jats:sup>\n                      macrophages and decreased fibroblast activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pharmacological inhibition of TBK1 with GSK8612 confers dual organ protection, attenuating both kidney and heart inflammation and fibrosis in a murine model of salt\u2010sensitive hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nep.70166","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T23:31:07Z","timestamp":1769124667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting\n                    <scp>TBK1<\/scp>\n                    With\n                    <scp>GSK8612<\/scp>\n                    Suppresses Kidney and Cardiac Inflammation and Fibrosis in\n                    <scp>DOCA<\/scp>\n                    \/Salt Hypertension"],"prefix":"10.1111","volume":"31","author":[{"given":"Jiamin","family":"Huang","sequence":"first","affiliation":[{"name":"The Second School of Clinical Medicine Southern Medical University  Guangzhou China"},{"name":"Department of Anesthesiology, Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Tenth Affiliated Hospital Southern of Medical University (Dongguan People's Hospital)  Dongguan China"},{"name":"Shenzhen School of Clinical Medicine Shenzhen Hospital, Southern Medical University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangquan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7406-8268","authenticated-orcid":false,"given":"Haihui","family":"Xie","sequence":"additional","affiliation":[{"name":"Department 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