The effect of cholesterol overload on mouse kidney and kidney-derived cells

Shoko Honzumi, Miho Takeuchi, Mizuki Kurihara, Masachika Fujiyoshi, Masashi Uchida, Kenta Watanabe, Takaaki Suzuki, Itsuko Ishii

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Introduction: Dyslipidemia is one of the onset and risk factors of chronic kidney disease and renal function drop is seen in lipoprotein abnormal animal models. However, the detailed molecular mechanism of renal lipotoxicity has not been clarified. Therefore, the present study aimed to investigate the influence of cholesterol overload using mouse kidney tissue and kidneyderived cultured cells. Methods: C57BL/6 mice were fed normal diet (ND) or 1.25% cholesterol-containing high-cholesterol diet (HCD) for 11 weeks, and we used megalin as a proximal tubule marker for immunohistology. We added beta-very low density lipoprotein (bVLDL) to kidney-derived cells and examined the effect of cholesterol overload on megalin protein and mRNA expression level, cell proliferation and cholesterol content in cells. Results: In the kidney of HCD mice, the gap between glomerulus and the surrounding Bowman’s capsule decreased and the expression level of megalin decreased. After bVLDL treatment to the cells, the protein expression and mRNA expression level of megalin decreased and cell proliferation was restrained. We also observed an increase in cholesterol accumulation in the cell and free cholesterol/phospholipid ratios increased. Conclusions: These findings suggest that the increased cholesterol load on kidney contribute to the decrease of megalin and the overloaded cholesterol is taken into the renal tubule epithelial cells, causing suppression on cell proliferation, which may be the cause of kidney damage.

Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalRenal failure
Issue number1
Publication statusPublished - Oct 15 2018


  • Beta-very low density lipoprotein
  • Dyslipidemia
  • Megalin
  • Renal lipotoxicity
  • Renal proximal tubule epithelial cell

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Nephrology


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