title: Activation of renin-angiotensin system is involved in dyslipidemia-mediated renal injuries in apolipoprotein E knockout mice and HK-2 cells.
abstract: BACKGROUND
  Dyslipidemia and activation of renin-angiotensin system (RAS) contribute to the progression of chronic kidney disease (CKD). This study investigated possible synergistic effects of intrarenal RAS activation with hyperlipidemia in renal injuries.
  
  
  METHODS
  Apolipoprotein knockout mice were fed with normal chow diet (control) or high fat diet (HF group) for eight weeks. Human proximal tubular epithelial cell line (HK-2) was treated without (control) or with cholesterol (30 μg/ml) plus 25-hydroxycholesterol (1 μg/ml) (lipid group) for 24 hours. The plasma lipid profile and RAS components were determined by clinical biochemistry assay and radiommunoassay, respectively. Collagen deposition in kidneys was evaluated by Masson-staining. The gene and protein expressions of molecules involved in RAS components and biomarkers of epithelial mesenchymal transition (EMT) were examined by real-time PCR, immunochemical staining, and Western blot.
  
  
  RESULTS
  The mice fed with high-fat diet showed significant hyperlipidemia with collagen deposition in renal tubular interstitium compared to controls. The plasma levels of renin, angiotensin I, and angiotensin II were no difference in two groups. However, the kidneys of HF group showed up-regulated RAS components, which were positively associated with increased plasma levels of triglyceride, total cholesterol, and LDL. These effects were further confirmed by in vitro studies. Lipid loading induced HK-2 cells underwent EMT, which was closely associated with the increased expressions of intracellular RAS components.
  
  
  CONCLUSIONS
  Local RAS activation was involved in hyperlipidemia-mediated renal injuries, suggesting that there are synergistic effects resulting from RAS activation with hyperlipidemia that accelerates the progression of CKD.
authors.forename: Jie
authors.initials: J
authors.lastname: Ni
authors.forename: Kun-Ling
authors.initials: KL
authors.lastname: Ma
authors.forename: Chang-Xian
authors.initials: CX
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lin-Li
authors.initials: LL
authors.lastname: Lv
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Ni
authors.forename: Ya-Xi
authors.initials: YX
authors.lastname: Chen
authors.forename: Xiong-Zhong
authors.initials: XZ
authors.lastname: Ruan
authors.forename: Bi-Cheng
authors.initials: BC
authors.lastname: Liu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects; D050171:Dyslipidemias / Q000150:complications* / Q000503:physiopathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D018345:Mice, Knockout; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E; D015820:Cadherins; D006888:Hydroxycholesterols; C007997:25-hydroxycholesterol; D002784:Cholesterol