{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:11:41Z","timestamp":1790079101371,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    To investigate the modulatory role of NOTCH3 in renal inflammatory and fibrotic processes during diabetic nephropathy (DN), focusing on TLR4\/NF\u2010\u03baB and TGF\u2010\u03b21\/Smad3 signaling pathways. HK2 cells were stimulated with BSA to mimic diabetic conditions\n                    <jats:italic>in vitro<\/jats:italic>\n                    . To investigate the roles of TLR4\/NF\u2010\u03baB and TGF\u2010\u03b21\/Smad3 pathways, cells were treated with Resatorvid or LPS, and SB\u2010431542 or TGF\u2010\u03b21, respectively. Also, HK2 cells were transfected with siRNA knockdown and pcDNA 3.1 overexpression vectors targeting NOTCH3. After treatments, cell viability, LDH release, inflammatory factors, apoptosis, and levels of fibrotic markers were analyzed. BSA stimulation upregulated NOTCH3 expression in HK2 cells. Silencing NOTCH3 enhanced viability and reduced LDH release, secretion of inflammatory factors, apoptosis, and fibrotic marker expression. Conversely, NOTCH3 overexpression exacerbated BSA\u2010induced cellular injury, inflammatory responses, and fibrotic marker expression. NOTCH3 also enhanced activation of the TLR4\/NF\u2010\u03baB and TGF\u2010\u03b21\/Smad3 pathways, and inhibition of either pathway partially mitigated the effects of NOTCH3 overexpression. Furthermore, in NOTCH3 knockdown cells, co\u2010treatment with downstream activators partially restored inflammatory and fibrotic responses, supporting the modulatory role of NOTCH3 in coordinating these signaling pathways. NOTCH3 modulates renal inflammation and fibrosis in BSA\u2010stimulated HK2 cells via the TLR4\/NF\u2010\u03baB and TGF\u2010\u03b21\/Smad3 pathways, highlighting its potential as a modulator of inflammatory and fibrotic responses in DN.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70984","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:02:35Z","timestamp":1783317755000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["NOTCH3 Modulates Inflammation and Fibrosis in HK2 Cells Under Diabetic Conditions Through TLR4\/NF\u2010\u03baB and TGF\u2010\u03b21\/Smad3 Signaling"],"prefix":"10.1002","volume":"40","author":[{"given":"RunHua","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory The Affiliated Hospital of Qingdao University Qingdao City Shandong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8355-6750","authenticated-orcid":false,"given":"ChunXi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Qingdao Women and Children's Hospital Qingdao City Shandong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.4.110807.092150"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450123666220820110801"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082806"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.661185"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1731"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom9110692"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.54"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/1809408"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23020884"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.01.031"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20051103"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2018.12.021"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.7.1056"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2020.151941"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-020-00747-z"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.666354"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.50893"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.95796"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920021705160324165553"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.05.012"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.578260"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034824"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019121289"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.48679"},{"issue":"10","key":"e_1_2_10_26_1","first-page":"5592","article-title":"MiR\u2010201\u20105p Alleviates Lipopolysaccharide\u2010Induced Renal Cell Dysfunction by Targeting Notch3","volume":"24","author":"Yuan Y. 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