{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:06:10Z","timestamp":1791770770037,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":332,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["20180540105"],"award-info":[{"award-number":["20180540105"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZSM202211013"],"award-info":[{"award-number":["SZSM202211013"]}],"id":[{"id":"10.13039\/501100012151","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":[[2025,1]]},"abstract":"<jats:p>\n                    Artemether (Art) is a derivative of artemisinin, originally sourced from traditional Chinese herbal medicine, with improved bioavailability, and is widely used for malaria treatment. Recently, its potential effects on diabetic complications, particularly diabetic kidney disease (DKD), have attracted increasing attention. This study aimed to evaluate the therapeutic effects of Art on DKD and to explore the underlying mechanisms. Specifically, we investigated the protective role of Art against high glucose (HG)\u2010induced inflammatory biomarkers (transforming growth factor\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1 [TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1], tumor necrosis factor\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    [TNF\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    ], interleukin\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    [IL\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ], and interleukin\u20106 [IL\u20106]) and fibrosis in human renal proximal tubular epithelial (HK\u20102) cells, focusing on the involvement of peroxisome proliferator\u2010activated receptor gamma (PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    ) in DKD. To mimic diabetic conditions, HK\u20102 cells were exposed to HG (30\u2009mM) to induce inflammation and fibrosis. The therapeutic effects of Art (100 and 200\u2009\n                    <jats:italic>\u03bc<\/jats:italic>\n                    m) were assessed by immunofluorescence, real\u2010time RT\u2010PCR, and Western blot analyses. Our results demonstrated that Art effectively reversed the HG\u2010induced upregulation of inflammatory and fibrogenic markers in HK\u20102 cells (\u2217\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05, \u2217\u2217\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001, and \u2009\n                    <jats:sup>##<\/jats:sup>\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001). Additionally, Art pretreatment restored the HG\u2010suppressed expression of PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    (\u2217\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05 and \u2009\n                    <jats:sup>##<\/jats:sup>\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001), suggesting that Art exerts its antifibrotic effects by modulating PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    and inhibiting the TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \/Smad pathway. This hypothesis was further supported by siRNA\u2010mediated knockdown of PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    , which significantly diminished Art\u2032s antifibrotic effects (\u2217\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05, \u2217\u2217\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001, and \u2009\n                    <jats:sup>##<\/jats:sup>\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001). In conclusion, our study indicates that Art protects renal tubular epithelial cells by partially modulating PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    \u2010dependent inhibition of the TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \/Smad pathway, thereby mitigating HG\u2010induced inflammation and fibrosis. These findings suggest that Art holds promising therapeutic potential for DKD treatment.\n                  <\/jats:p>","DOI":"10.1155\/jdr\/5052561","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T08:37:07Z","timestamp":1764405427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Artemether Attenuates High Glucose\u2010Induced Inflammation and Fibrogenesis in Renal Tubular Epithelial Cells by Modulating the TGF\u2010\n                    <i>\u03b2<\/i>\n                    \/Smad Pathway Via PPAR\n                    <i>\u03b3<\/i>\n                    Activation"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8123-8288","authenticated-orcid":false,"given":"Xiuli","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingzhi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1504-7842","authenticated-orcid":false,"given":"Zhihong","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-018-0001-y"},{"key":"e_1_2_15_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-01922"},{"key":"e_1_2_15_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joim.2022.07.004"},{"key":"e_1_2_15_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s43657-022-00074-x"},{"key":"e_1_2_15_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0234-4"},{"key":"e_1_2_15_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21121656"},{"key":"e_1_2_15_7_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2418671"},{"key":"e_1_2_15_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00737"},{"key":"e_1_2_15_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.01.009"},{"key":"e_1_2_15_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-014-0977-0"},{"key":"e_1_2_15_11_2","first-page":"1389","article-title":"Artemether 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