{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T01:46:29Z","timestamp":1793497589897,"version":"4.5.0"},"reference-count":66,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"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>Hypertension and obesity are well-established risk factors for chronic kidney disease (CKD). This study investigates the interaction between these two factors in CKD using animal models. Twelve-week-old normotensive Wistar Kyoto (WKY), spontaneously hypertensive (SHR), and stroke-prone spontaneously hypertensive (SHR-SP) rats were fed either a normal diet (control) or a high-fat diet (HFD) for eight weeks. Kidney pathology and molecular mechanisms were assessed via immunostaining, real-time PCR, and Western blotting. In the control-fed groups, SHR-SP showed the most severe glomerular and tubular fibrosis, followed by SHR. The HFD exacerbated fibrosis in both the WKY and SHR rats but not in the SHR-SP rats. The levels of the mesangial marker smooth muscle \u03b1-actin (SMA) in the glomeruli were highest in the control-fed SHR-SP rats. HFD feeding increased glomerular SMA levels in WKY and SHR but not in SHR-SP. The levels of the mesenchymal marker vimentin were elevated in the control-fed SHR-SP rats compared to the other control-fed animals. The HFD increased the vimentin levels in WKY but decreased them in SHR-SP. The HFD increased senescence and inflammatory markers in the kidneys of the WKY and SHR rats. The HFD-fed WKY and SHR rats also showed upregulation of platelet-derived growth factor \u03b2 (PDGF\u03b2) signaling molecules. Among the control-fed animals, the transforming growth factor \u03b2 (TGF\u03b2) and TGF\u03b2 receptor 2 (TGF\u03b2R2) levels were elevated in SHR-SP. HFD feeding increased the TGF\u03b2R2 levels in WKY and the SHR and TGF\u03b2 levels in WKY. Similarly, SMAD2\/3 activation was the highest in the SHR-SP control group. HFD feeding increased the SMAD2\/3 activation in the kidneys of the WKY and SHR rats. Thus, our findings demonstrate that a high-fat diet can intensify renal fibrosis independent of hypertension through TGF\u03b2 and PDGF\u03b2 signaling within a two-month timeframe.<\/jats:p>","DOI":"10.3390\/ijms26168031","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T08:02:44Z","timestamp":1755763364000},"page":"8031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A High-Fat Diet Increases Kidney Fibrosis Through Regulating TGF-\u03b2 and PDGF-\u03b2 Signaling Pathways in Normotensive and Hypertensive Rat Models"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3261-6328","authenticated-orcid":false,"given":"Fatema Binte","family":"Abdullah","sequence":"first","affiliation":[{"name":"Department of Nephrology, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1221-7787","authenticated-orcid":false,"given":"Abdullah Md.","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shatera","family":"Tabassum","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9280-8044","authenticated-orcid":false,"given":"Atsushi","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9833-4356","authenticated-orcid":false,"given":"Jun","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Nabika","sequence":"additional","affiliation":[{"name":"School of Nursing, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9210-2949","authenticated-orcid":false,"given":"Shozo","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/jch.14186","article-title":"Chronic kidney disease: Definition, updated epidemiology, staging, and mechanisms of increased cardiovascular risk","volume":"23","author":"Wilson","year":"2021","journal-title":"J. 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