Targeting ROS and cPLA2/COX2 Expressions Ameliorated Renal Damage in Obese Mice with Endotoxemia
Journal
International journal of molecular sciences
Journal Volume
20
Journal Issue
18
Date Issued
2019-09
Author(s)
Chang, Jia-Feng
Yeh, Jih-Chen
Ho, Chun-Ta
Liu, Shih-Hao
Hsieh, Chih-Yu
Lee, I.-Ta
Huang, Kuo-Yang
Wang, Jen-Yu
Lin, Wei-Ning
Abstract
Obesity is associated with metabolic endotoxemia, reactive oxygen species (ROS), chronic inflammation, and obese kidney fibrosis. Although the fat-intestine-kidney 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-metabolic 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-ROS could serve as a potential therapeutic target of obese kidney fibrosis with metabolic endotoxemia. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
cPLA2 and COX-2
Endotoxemia
Obese kidney fibrosis
ROS
SDGs
Type
journal article