{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:21:20Z","timestamp":1791415280952,"version":"4.3.3"},"reference-count":36,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":44,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81600643"],"award-info":[{"award-number":["81600643"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"China Endocrine Metabolism Talent Research Fund","award":["2022-N-02-07,2023-N-03-15"],"award-info":[{"award-number":["2022-N-02-07,2023-N-03-15"]}]},{"name":"Scientific Research Funding of Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin Key Laboratory of Metabolic Diseases","award":["ZXY-ZDSYSZD2022-1"],"award-info":[{"award-number":["ZXY-ZDSYSZD2022-1"]}]},{"DOI":"10.13039\/100016966","name":"Bethune Charitable Foundation","doi-asserted-by":"crossref","award":["Z04JKM2022E035"],"award-info":[{"award-number":["Z04JKM2022E035"]}],"id":[{"id":"10.13039\/100016966","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hubei Chen Xiaoping Science and Technology Development Fund","award":["CXPJJH122012-002"],"award-info":[{"award-number":["CXPJJH122012-002"]}]},{"name":"Scientific Research Program of Tianjin Education Commission","award":["2022KJ248"],"award-info":[{"award-number":["2022KJ248"]}]},{"name":"Tianjin Key Medical Discipline (Specialty) Construction Project","award":["TJYXZDXK-032A"],"award-info":[{"award-number":["TJYXZDXK-032A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,23]]},"abstract":"<jats:p>\n                    Diabetes mellitus (DM) is acknowledged as an independent risk factor for acute kidney injury. Ras guanine nucleotide-releasing protein-4 (\n                    <jats:italic>RasGRP4<\/jats:italic>\n                    ) exerts a notable role in modulating immune-inflammatory responses and kidney disease progression in diabetes. Herein, we delved into the specific role and mechanism of\n                    <jats:italic>RasGRP4<\/jats:italic>\n                    in diabetic renal ischemia-reperfusion injury. Diabetes was induced by a high-fat diet and streptozocin (STZ) injections, followed by creating an ischemia-reperfusion kidney injury via renal pedicle clamping and reperfusion. In vitro, a high glucose and hypoxia-reoxygenation modeled cellular inflammatory injury. We found\n                    <jats:italic>RasGRP4<\/jats:italic>\n                    -KO mice, compared with C57BL\/6J (WT) mice, showed markedly less renal dysfunction and fibrosis in diabetic ischemia-reperfusion injury. There was a significant decrease in the renal infiltration of M1 macrophages and Th17 cells, along with downregulated IL-17 pathway proteins and effectors. In vitro,\n                    <jats:italic>RasGRP4<\/jats:italic>\n                    deletion restrained M1 macrophage polarization and Th17 cell differentiation, inhibiting the IL-17 signaling pathway in HK-2 cells. Hyperglycemia intensified renal inflammation state. Together,\n                    <jats:italic>RasGRP4<\/jats:italic>\n                    , through the regulation of interactions among M1 macrophages, CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and HK-2 cells, formed a cascade that intensified the inflammatory storm activity, ultimately exacerbating the inflammatory injury of diabetic ischemia-reperfusion kidneys. DM intensified this inflammatory injury mechanism, worsening the injury from renal ischemia-reperfusion.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.187653","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T12:02:23Z","timestamp":1733832143000},"source":"Crossref","is-referenced-by-count":9,"title":["RasGRP4 aggravates ischemia-reperfusion injury in diabetic kidneys by mediating communication between macrophages and T cells"],"prefix":"10.1172","volume":"10","author":[{"given":"Li","family":"Zhang","sequence":"first","affiliation":[{"name":"NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases,Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanglong","family":"Wang","sequence":"additional","affiliation":[{"name":"NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic 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