Targeting ROS and cPLA2/COX2 Expressions Ameliorated Renal Damage in Obese Mice with Endotoxemia

Jia Feng Chang, Jih Chen Yeh, Chun Ta Ho, Shih Hao Liu, Chih Yu Hsieh, Ting Ming Wang, Shu Wei Chang, I. Ta Lee, Kuo Yang Huang, Jen Yu Wang, Wei Ning Lin

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume20
Issue number18
DOIs
Publication statusPublished - Sep 6 2019

Keywords

  • cPLA2 and COX-2
  • endotoxemia
  • obese kidney fibrosis
  • ROS

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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    Chang, J. F., Yeh, J. C., Ho, C. T., Liu, S. H., Hsieh, C. Y., Wang, T. M., Chang, S. W., Lee, I. T., Huang, K. Y., Wang, J. Y., & Lin, W. N. (2019). Targeting ROS and cPLA2/COX2 Expressions Ameliorated Renal Damage in Obese Mice with Endotoxemia. International Journal of Molecular Sciences, 20(18). https://doi.org/10.3390/ijms20184393