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Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction.

Asahina M, Shimizu F, Ohta M, Takeyama M, Tozawa R - Exp. Anim. (2015)

Bottom Line: They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers.Histological analyses revealed the characteristic features of human apoB Tg.Our newly established human apoB Tg.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa 251-8555, Japan.

ABSTRACT
Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome.

No MeSH data available.


Related in: MedlinePlus

Representative light micrographs of H&E- (A-D), PAM- (E-H), and Oil RedO-stained (I, J) kidney sections from 36-week-old human apoB Tg.SHR-cp/cp (A, E, I), non-Tg. SHR-cp/cp (B, F,J), human apoB Tg. SHR-+/+ (C, G), and non-Tg. SHR-+/+ rats (D, H). Filled circlesindicate hyaline casts. Arrows indicate dilated tubules. In the sections stainedwith Oil Red O (I, J), lipid droplets appeared as red spots and indicate theaccumulation of neutral lipids in the glomeruli. K: The glomerulosclerosis scoreof the rats is shown. The number of rats is shown in parentheses. Values are shownas the mean ± SEM. Bars=100 μm. The asterisks indicate asignificant difference at ††P<0.01 compared withthe human apoB Tg. SHR-cp/cp rats.
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fig_003: Representative light micrographs of H&E- (A-D), PAM- (E-H), and Oil RedO-stained (I, J) kidney sections from 36-week-old human apoB Tg.SHR-cp/cp (A, E, I), non-Tg. SHR-cp/cp (B, F,J), human apoB Tg. SHR-+/+ (C, G), and non-Tg. SHR-+/+ rats (D, H). Filled circlesindicate hyaline casts. Arrows indicate dilated tubules. In the sections stainedwith Oil Red O (I, J), lipid droplets appeared as red spots and indicate theaccumulation of neutral lipids in the glomeruli. K: The glomerulosclerosis scoreof the rats is shown. The number of rats is shown in parentheses. Values are shownas the mean ± SEM. Bars=100 μm. The asterisks indicate asignificant difference at ††P<0.01 compared withthe human apoB Tg. SHR-cp/cp rats.

Mentions: Representative histological features of 36-week-old male human apoB Tg.SHR-cp/cp rats are shown in Fig. 3Fig. 3.


Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction.

Asahina M, Shimizu F, Ohta M, Takeyama M, Tozawa R - Exp. Anim. (2015)

Representative light micrographs of H&E- (A-D), PAM- (E-H), and Oil RedO-stained (I, J) kidney sections from 36-week-old human apoB Tg.SHR-cp/cp (A, E, I), non-Tg. SHR-cp/cp (B, F,J), human apoB Tg. SHR-+/+ (C, G), and non-Tg. SHR-+/+ rats (D, H). Filled circlesindicate hyaline casts. Arrows indicate dilated tubules. In the sections stainedwith Oil Red O (I, J), lipid droplets appeared as red spots and indicate theaccumulation of neutral lipids in the glomeruli. K: The glomerulosclerosis scoreof the rats is shown. The number of rats is shown in parentheses. Values are shownas the mean ± SEM. Bars=100 μm. The asterisks indicate asignificant difference at ††P<0.01 compared withthe human apoB Tg. SHR-cp/cp rats.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4548004&req=5

fig_003: Representative light micrographs of H&E- (A-D), PAM- (E-H), and Oil RedO-stained (I, J) kidney sections from 36-week-old human apoB Tg.SHR-cp/cp (A, E, I), non-Tg. SHR-cp/cp (B, F,J), human apoB Tg. SHR-+/+ (C, G), and non-Tg. SHR-+/+ rats (D, H). Filled circlesindicate hyaline casts. Arrows indicate dilated tubules. In the sections stainedwith Oil Red O (I, J), lipid droplets appeared as red spots and indicate theaccumulation of neutral lipids in the glomeruli. K: The glomerulosclerosis scoreof the rats is shown. The number of rats is shown in parentheses. Values are shownas the mean ± SEM. Bars=100 μm. The asterisks indicate asignificant difference at ††P<0.01 compared withthe human apoB Tg. SHR-cp/cp rats.
Mentions: Representative histological features of 36-week-old male human apoB Tg.SHR-cp/cp rats are shown in Fig. 3Fig. 3.

Bottom Line: They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers.Histological analyses revealed the characteristic features of human apoB Tg.Our newly established human apoB Tg.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa 251-8555, Japan.

ABSTRACT
Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome.

No MeSH data available.


Related in: MedlinePlus