{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T22:20:22Z","timestamp":1769552422225,"version":"3.49.0"},"reference-count":48,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,6]],"date-time":"2019-09-06T00:00:00Z","timestamp":1567728000000},"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>Obesity is associated with metabolic endotoxemia, reactive oxygen species (ROS), chronic inflammation, and obese kidney fibrosis. Although the fat\u2013intestine\u2013kidney axis has been documented, the pathomechanism and therapeutic targets of obese kidney fibrosis remain unelucidated. To mimic obese humans with metabolic endotoxemia, high-fat-diet-fed mice (HF group) were injected with lipopolysaccharide (LPS) to yield the obese kidney fibrosis\u2013metabolic endotoxemia mouse model (HL group). Therapeutic effects of ROS, cytosolic phospholipases A2 (cPLA2) and cyclooxygenase-2 (COX-2) inhibitors were analyzed with a quantitative comparison of immunohistochemistry stains and morphometric approach in the tubulointerstitium of different groups. Compared with basal and HF groups, the HL group exhibited the most prominent obese kidney fibrosis, tubular epithelial lipid vacuoles, and lymphocyte infiltration in the tubulointerstitium. Furthermore, inhibitors of nonspecific ROS, cPLA2 and COX-2 ameliorated the above renal damages. Notably, the ROS-inhibitor-treated group ameliorated not only oxidative injury but also the expression of cPLA2 and COX-2, indicating that ROS functions as the upstream signaling molecule in the inflammatory cascade of obese kidney fibrosis. ROS acts as a key messenger in the signaling transduction of obese kidney fibrosis, activating downstream cPLA2 and COX-2. The given antioxidant treatment ameliorates obese kidney fibrosis resulting from a combined high-fat diet and LPS\u2014ROS could serve as a potential therapeutic target of obese kidney fibrosis with metabolic endotoxemia.<\/jats:p>","DOI":"10.3390\/ijms20184393","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T03:14:41Z","timestamp":1567998881000},"page":"4393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Targeting ROS and cPLA2\/COX2 Expressions Ameliorated Renal Damage in Obese Mice with Endotoxemia"],"prefix":"10.3390","volume":"20","author":[{"given":"Jia-Feng","family":"Chang","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, En Chu Kong Hospital, New Taipei City 237, Taiwan"},{"name":"Renal Care Joint Foundation, New Taipei City 220, Taiwan"},{"name":"Department of Nursing, Yuanpei University of Medical Technology, Hsinchu 300, Taiwan"},{"name":"Graduate Institution of Biomedical and Pharmaceutical Science, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jih-Chen","family":"Yeh","sequence":"additional","affiliation":[{"name":"Renal Care Joint Foundation, New Taipei City 220, Taiwan"},{"name":"Department of Dentistry, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Ta","family":"Ho","sequence":"additional","affiliation":[{"name":"Renal Care Joint Foundation, New Taipei City 220, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Pathology, En-Chu-Kong Hospital, New Taipei City 237, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9770-6779","authenticated-orcid":false,"given":"Chih-Yu","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, En Chu Kong Hospital, New Taipei City 237, Taiwan"},{"name":"Renal Care Joint Foundation, New Taipei City 220, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2263-5993","authenticated-orcid":false,"given":"Ting-Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, School of Medicine, National Taiwan University, Taipei 106, Taiwan"},{"name":"Department of Orthopaedic Surgery, National Taiwan University Hospital, Taipei 106, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Wei","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Civil Engineering, National Taiwan University, Taipei 106, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I-Ta","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4038-1579","authenticated-orcid":false,"given":"Kuo-Yang","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jen-Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate Institution of Biomedical and Pharmaceutical Science, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3205-871X","authenticated-orcid":false,"given":"Wei-Ning","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institution of Biomedical and Pharmaceutical Science, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1681\/ASN.2013040330","article-title":"Obesity in CKD\u2014What should nephrologists know?","volume":"24","author":"Stenvinkel","year":"2013","journal-title":"J. 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