{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T15:32:09Z","timestamp":1794324729495,"version":"4.9.0"},"reference-count":78,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>\n                    c-Jun N-terminal kinase (JNK) contributes to the pathogenesis of diabetic nephropathy (DN). The JNK inhibitor SP600125 was reported to ameliorate DN. However, the mechanism remained unclear. We previously reported that SP600125 activated nuclear factor erythroid 2-related factor 2 (NRF2), a governor of the cellular antioxidant defense system, in the aortas of the diabetic mice. Given the critical role of NRF2 in preventing DN, the present study aimed to test whether or not NRF2 is required for SP600125\u2019s protection against DN. To test the role of NRF2 in SP600125\u2019s effect, streptozotocin-induced C57BL\/6 wild-type (WT) and\n                    <jats:italic>Nrf2<\/jats:italic>\n                    -knockout (KO) diabetic mice were treated in the presence or absence of SP600125, for 24 weeks. To explore the mechanism by which SP600125 activates NRF2, mouse mesangial cells (MMCs) were treated with high glucose (HG), in the presence or absence of either SP600125 or JNK siRNA. SP600125 significantly attenuated the diabetes-induced renal oxidative stress, inflammation, fibrosis, pathological change and dysfunction in the WT, but not the\n                    <jats:italic>Nrf2<\/jats:italic>\n                    KO mice. SP600125 inactivated JNK, inhibited kelch-like ECH-associated protein 1 expression, preserved NRF2 protein and facilitated its nuclear translocation in the kidneys of the WT mice, the effects of which were similarly produced by either SP600125 or JNK siRNA in HG-treated MMCs. Further, both SP600125 and JNK siRNA alleviated HG-induced mesangial oxidative stress and expression of inflammatory and fibrotic genes. The present study demonstrates that NRF2 is required for SP600125\u2019s protection against DN. SP600125 activates NRF2 possibly via inhibition of JNK-induced\n                    <jats:italic>Keap1<\/jats:italic>\n                    expression.\n                  <\/jats:p>","DOI":"10.1530\/jme-17-0260","type":"journal-article","created":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T20:20:38Z","timestamp":1513974038000},"page":"145-157","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":36,"title":["SP600125 suppresses Keap1 expression and results in NRF2-mediated prevention of diabetic nephropathy"],"prefix":"10.1530","volume":"60","author":[{"given":"Huan","family":"Zhang","sequence":"first","affiliation":[{"name":"1Operating Theater, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxia","family":"Liu","sequence":"additional","affiliation":[{"name":"2Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, Jilin, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhou","sequence":"additional","affiliation":[{"name":"3Cardiovascular Center, The First Hospital of Jilin University, Changchun, Jilin, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Jia","sequence":"additional","affiliation":[{"name":"4Department of Nephrology, The First Hospital of Jilin University, Changchun, Jilin, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"5Department of Dermatology, Affiliated Hospital of Beihua University, Jilin, Jilin, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguo","family":"Song","sequence":"additional","affiliation":[{"name":"6Research Institute of Clinical Immunology, Affiliated Hospital of Beihua University, Jilin, Jilin, People\u2019s Republic of China"},{"name":"7Research Center for Life Sciences, Beihua University, Jilin, Jilin, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junnan","family":"Wang","sequence":"additional","affiliation":[{"name":"8Department of Cardiology, The Second Hospital of Jilin University, Changchun, Jilin, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"9Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin, People\u2019s Republic of China"},{"name":"10The \u2018973\u2019 National Basic Research Program of China, Changchun University of Chinese Medicine, Changchun, Jilin, People\u2019s Republic of 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