Abstract
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 language | English |
|---|---|
| Pages (from-to) | 43-50 |
| Number of pages | 8 |
| Journal | Renal Failure |
| Volume | 40 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Oct 15 2018 |
| Externally published | Yes |
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Keywords
- 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
Cite this
The effect of cholesterol overload on mouse kidney and kidney-derived cells. / Honzumi, Shoko; Takeuchi, Miho; Kurihara, Mizuki; Fujiyoshi, Masachika; Uchida, Masashi; Watanabe, Kenta; Suzuki, Takaaki; Ishii, Itsuko.
In: Renal Failure, Vol. 40, No. 1, 15.10.2018, p. 43-50.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The effect of cholesterol overload on mouse kidney and kidney-derived cells
AU - Honzumi, Shoko
AU - Takeuchi, Miho
AU - Kurihara, Mizuki
AU - Fujiyoshi, Masachika
AU - Uchida, Masashi
AU - Watanabe, Kenta
AU - Suzuki, Takaaki
AU - Ishii, Itsuko
PY - 2018/10/15
Y1 - 2018/10/15
N2 - 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.
AB - 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.
KW - Beta-very low density lipoprotein
KW - Dyslipidemia
KW - Megalin
KW - Renal lipotoxicity
KW - Renal proximal tubule epithelial cell
UR - http://www.scopus.com/inward/record.url?scp=85046884343&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046884343&partnerID=8YFLogxK
U2 - 10.1080/0886022X.2017.1419974
DO - 10.1080/0886022X.2017.1419974
M3 - Article
C2 - 29304720
AN - SCOPUS:85046884343
VL - 40
SP - 43
EP - 50
JO - Renal Failure
JF - Renal Failure
SN - 0886-022X
IS - 1
ER -