{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:24:25Z","timestamp":1792686265388,"version":"4.5.0"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:00:00Z","timestamp":1592524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dysregulation of fatty acid oxidation and accumulation of fatty acids can cause kidney injury. Nifedipine modulates lipogenesis-related transcriptional factor SREBP-1\/2 in proximal tubular cells by inhibiting the Adenosine 5\u2018-monophosphate (AMP)-activated protein kinase (AMPK) pathway in vitro. However, the mechanisms by which nifedipine (NF) modulates lipotoxicity in vivo are unclear. Here, we examined the effect of NF in a doxorubicin (DR)-induced kidney injury rat model. Twenty-four Sprague\u2013Dawley rats were divided into control, DR, DR+NF, and high-fat diet (HFD) groups. The DR, DR+NF, and HFD groups showed hypertension and proteinuria. Western blotting and immunohistochemical analysis showed that NF significantly induced TNF-\u03b1, CD36, SREBP-1\/2, and acetyl-CoA carboxylase expression and renal fibrosis, and reduced fatty acid synthase and AMPK compared to other groups (p &lt; 0.05). Additionally, 18 patients with chronic kidney disease (CKD) who received renal transplants were enrolled to examine their graft fibrosis and lipid contents via transient elastography. Low-density lipoprotein levels in patients with CKD strongly correlated with lipid contents and fibrosis in grafted kidneys (p &lt; 0.05). Thus, NF may initiate lipogenesis through the SREBP-1\/2\/AMPK pathway and lipid uptake by CD36 upregulation and aggravate renal fibrosis in vivo. Higher low-density lipoprotein levels may correlate with renal fibrosis and lipid accumulation in grafted kidneys of patients with CKD.<\/jats:p>","DOI":"10.3390\/ijms21124359","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T10:43:58Z","timestamp":1592563438000},"page":"4359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Nifedipine Exacerbates Lipogenesis in the Kidney via KIM-1, CD36, and SREBP Upregulation: Implications from an Animal Model for Human Study"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8981-8671","authenticated-orcid":false,"given":"Yen-Chung","family":"Lin","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"TMU-Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhih-Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Chi-Mei Medical Center, Tainan City 71004, Taiwan"},{"name":"Department of Electric Engineering, Southern Taiwan University of Science and Technology, Tainan City 71005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai-Szu","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"TMU-Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7861-5054","authenticated-orcid":false,"given":"Yuh-Feng","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"TMU-Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Rong","family":"Chen","sequence":"additional","affiliation":[{"name":"International Medical Doctor Program, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Program of Biomedical Sciences, College of Arts and Sciences, California Baptist University, Riverside, CA 92504, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5512-4631","authenticated-orcid":false,"given":"Kuan-Chou","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"TMU-Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Department of Urology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan"},{"name":"Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiung-Chi","family":"Peng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S2213-8587(14)70065-8","article-title":"Fatty kidney: Emerging role of ectopic lipid in obesity-related renal disease","volume":"2","author":"Ruggenenti","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/978-3-319-48382-5_8","article-title":"What is lipotoxicity?","volume":"960","author":"Engin","year":"2017","journal-title":"Adv. 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