Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the Pathology

Diabetic kidney disease (DKD) is a critical complication associated with diabetes; however, there are only a few animal models that can be used to explore its pathogenesis. In the present study, we established a mouse model of DKD using a technique based on the Developmental Origins of Health and Di...

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Main Authors: Shiori Ishiyama, Mayu Kimura, Takao Nakagawa, Yuka Fujimoto, Kohei Uchimura, Satoshi Kishigami, Kazuki Mochizuki
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2021.746838/full
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author Shiori Ishiyama
Mayu Kimura
Takao Nakagawa
Yuka Fujimoto
Kohei Uchimura
Satoshi Kishigami
Satoshi Kishigami
Kazuki Mochizuki
Kazuki Mochizuki
author_facet Shiori Ishiyama
Mayu Kimura
Takao Nakagawa
Yuka Fujimoto
Kohei Uchimura
Satoshi Kishigami
Satoshi Kishigami
Kazuki Mochizuki
Kazuki Mochizuki
author_sort Shiori Ishiyama
collection DOAJ
description Diabetic kidney disease (DKD) is a critical complication associated with diabetes; however, there are only a few animal models that can be used to explore its pathogenesis. In the present study, we established a mouse model of DKD using a technique based on the Developmental Origins of Health and Disease theory, i.e., by manipulating the embryonic environment, and investigated whether a dietary intervention could ameliorate the model’s pathology. Two-cell embryos were cultured in vitro in α-minimum essential medium (MEM; MEM mice) or in standard potassium simplex-optimized medium (KSOM) as controls (KSOM mice) for 48 h, and the embryos were reintroduced into the mothers. The MEM and KSOM mice born were fed a high-fat, high-sugar diet for 58 days after they were 8 weeks old. Subsequently, half of the MEM mice and all KSOM mice were fed a diet containing rice powder (control diet), and the remaining MEM mice were fed a diet containing barley powder (barley diet) for 10 weeks. Glomerulosclerosis and pancreatic exhaustion were observed in MEM mice, but not in control KSOM mice. Renal arteriolar changes, including intimal thickening and increase in the rate of hyalinosis, were more pronounced in MEM mice fed a control diet than in KSOM mice. Immunostaining showed the higher expression of transforming growth factor beta (TGFB) in the proximal/distal renal tubules of MEM mice fed a control diet than in those of KSOM mice. Pathologies, such as glomerulosclerosis, renal arteriolar changes, and higher TGFB expression, were ameliorated by barley diet intake in MEM mice. These findings suggested that the MEM mouse is an effective DKD animal model that shows glomerulosclerosis and renal arteriolar changes, and barley intake can improve these pathologies in MEM mice.
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spelling doaj.art-9460dd808d4f465080629a3c1920e0002022-12-21T19:09:57ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-11-011210.3389/fendo.2021.746838746838Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the PathologyShiori Ishiyama0Mayu Kimura1Takao Nakagawa2Yuka Fujimoto3Kohei Uchimura4Satoshi Kishigami5Satoshi Kishigami6Kazuki Mochizuki7Kazuki Mochizuki8Department of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, Kofu, JapanDepartment of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, Kofu, JapanKiwa Laboratory Animals Co., Ltd., Kiminocho, JapanAdvanced Biotechnology Center, University of Yamanashi, Kofu, JapanDivision of Nephrology, Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Kofu, JapanDepartment of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, Kofu, JapanFaculty of Life and Environmental Sciences, University of Yamanashi, Kofu, JapanDepartment of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, Kofu, JapanFaculty of Life and Environmental Sciences, University of Yamanashi, Kofu, JapanDiabetic kidney disease (DKD) is a critical complication associated with diabetes; however, there are only a few animal models that can be used to explore its pathogenesis. In the present study, we established a mouse model of DKD using a technique based on the Developmental Origins of Health and Disease theory, i.e., by manipulating the embryonic environment, and investigated whether a dietary intervention could ameliorate the model’s pathology. Two-cell embryos were cultured in vitro in α-minimum essential medium (MEM; MEM mice) or in standard potassium simplex-optimized medium (KSOM) as controls (KSOM mice) for 48 h, and the embryos were reintroduced into the mothers. The MEM and KSOM mice born were fed a high-fat, high-sugar diet for 58 days after they were 8 weeks old. Subsequently, half of the MEM mice and all KSOM mice were fed a diet containing rice powder (control diet), and the remaining MEM mice were fed a diet containing barley powder (barley diet) for 10 weeks. Glomerulosclerosis and pancreatic exhaustion were observed in MEM mice, but not in control KSOM mice. Renal arteriolar changes, including intimal thickening and increase in the rate of hyalinosis, were more pronounced in MEM mice fed a control diet than in KSOM mice. Immunostaining showed the higher expression of transforming growth factor beta (TGFB) in the proximal/distal renal tubules of MEM mice fed a control diet than in those of KSOM mice. Pathologies, such as glomerulosclerosis, renal arteriolar changes, and higher TGFB expression, were ameliorated by barley diet intake in MEM mice. These findings suggested that the MEM mouse is an effective DKD animal model that shows glomerulosclerosis and renal arteriolar changes, and barley intake can improve these pathologies in MEM mice.https://www.frontiersin.org/articles/10.3389/fendo.2021.746838/fulldiabetic kidney disease (DKD)MEM miceDOHaD (developmental origins of health and disease)barleyglomerulosclerosistransforming growth factor beta (TGF- β)
spellingShingle Shiori Ishiyama
Mayu Kimura
Takao Nakagawa
Yuka Fujimoto
Kohei Uchimura
Satoshi Kishigami
Satoshi Kishigami
Kazuki Mochizuki
Kazuki Mochizuki
Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the Pathology
Frontiers in Endocrinology
diabetic kidney disease (DKD)
MEM mice
DOHaD (developmental origins of health and disease)
barley
glomerulosclerosis
transforming growth factor beta (TGF- β)
title Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the Pathology
title_full Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the Pathology
title_fullStr Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the Pathology
title_full_unstemmed Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the Pathology
title_short Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the Pathology
title_sort development of the diabetic kidney disease mouse model culturing embryos in α minimum essential medium in vitro and feeding barley diet attenuated the pathology
topic diabetic kidney disease (DKD)
MEM mice
DOHaD (developmental origins of health and disease)
barley
glomerulosclerosis
transforming growth factor beta (TGF- β)
url https://www.frontiersin.org/articles/10.3389/fendo.2021.746838/full
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