Stem Cells from Human Exfoliated Deciduous Teeth Ameliorate Diabetic Nephropathy In Vivo and In Vitro by Inhibiting Advanced Glycation End Product-Activated Epithelial-Mesenchymal Transition
Diabetic nephropathy (DN) is a major cause of chronic kidney disease. It has been proven that mesenchymal stem cells (MSCs) have therapeutic effects on kidney disease. Stem cells from human exfoliated deciduous teeth (SHED) are MSCs that are derived from dental pulps in exfoliated deciduous teeth fr...
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| Language: | English |
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/2751475 |
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| author | Nanquan Rao Xiaotong Wang Jing Xie Jingzhi Li Yue Zhai Xiaoxia Li Tengjiaozi Fang Yuanyuan Wang Yuming Zhao Lihong Ge |
| author_facet | Nanquan Rao Xiaotong Wang Jing Xie Jingzhi Li Yue Zhai Xiaoxia Li Tengjiaozi Fang Yuanyuan Wang Yuming Zhao Lihong Ge |
| author_sort | Nanquan Rao |
| collection | DOAJ |
| description | Diabetic nephropathy (DN) is a major cause of chronic kidney disease. It has been proven that mesenchymal stem cells (MSCs) have therapeutic effects on kidney disease. Stem cells from human exfoliated deciduous teeth (SHED) are MSCs that are derived from dental pulps in exfoliated deciduous teeth from young patients and therefore have a high proliferation rate and an easy access. Hence, we aimed to explore the effect of SHED on DN in Goto-Kakizaki (GK) rats. SHED were administered via the tail vein. Blood glucose, serum triglycerides and cholesterol, body weight, and urinary albumin were measured before and after administration. At 8 weeks after administration, real-time PCR, immunohistochemistry (IHC), and electron microscopy were employed to examine pathological changes in glomerular and tubulointerstitial tissue. Kidney weight and serum IL-1, IL-10, TNF-α, TGF-β, and HGF levels were measured. SHED engraftment in the kidneys was detected by transfecting green fluorescence protein (GFP). Type II epithelial-mesenchymal transition (EMT) in the tubule-interstitial and arteriolar regions has been reported to be an important pathological characteristic of DN. This study is the first to apply a transwell system for coculture to explore the effects of MSCs on the EMT of human proximal tubular epithelial (HK-2) cells. The effects of SHED on advanced glycation end product- (AGE-) activated EMT in HK-2 cells were explored by real-time PCR and western blot. At 8 weeks after administration, renal injury, including hyperglycemia, hyperlipidemia, increased urinary albumin excretion, ECM accumulation, and a fractional mesangial area, was dramatically attenuated. The serum levels of IL-1, TNF-α, and TGF-β were significantly downregulated, whereas the serum levels of IL-10 and HGF were upregulated by SHED. GFP expression confirmed the engraftment of SHED in diabetic kidneys. In addition, cocultured SHED inhibited AGE-induced EMT in HK-2 cells. In conclusion, SHED offer a novel potential effective therapeutic approach for ameliorating DN. |
| format | Article |
| id | doaj-art-aaf7865a1f2c4e3d81e34777d75ed72a |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Stem Cells International |
| spelling | doaj-art-aaf7865a1f2c4e3d81e34777d75ed72a2025-02-03T06:01:27ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/27514752751475Stem Cells from Human Exfoliated Deciduous Teeth Ameliorate Diabetic Nephropathy In Vivo and In Vitro by Inhibiting Advanced Glycation End Product-Activated Epithelial-Mesenchymal TransitionNanquan Rao0Xiaotong Wang1Jing Xie2Jingzhi Li3Yue Zhai4Xiaoxia Li5Tengjiaozi Fang6Yuanyuan Wang7Yuming Zhao8Lihong Ge9Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, ChinaDepartment of Oral Emergency Department, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, ChinaDepartment of Stomatology, Shenzhen Children’s Hospital, No. 7019, Yitian Road, Shenzhen 518026, ChinaDepartment of Pediatric Dentistry, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, ChinaDepartment of Pediatric Dentistry, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, ChinaDepartment of Pediatric Dentistry, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, ChinaDepartment of Pediatric Dentistry, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, ChinaDepartment of Pediatric Dentistry, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, ChinaDepartment of Pediatric Dentistry, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, ChinaDepartment of Pediatric Dentistry, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, ChinaDiabetic nephropathy (DN) is a major cause of chronic kidney disease. It has been proven that mesenchymal stem cells (MSCs) have therapeutic effects on kidney disease. Stem cells from human exfoliated deciduous teeth (SHED) are MSCs that are derived from dental pulps in exfoliated deciduous teeth from young patients and therefore have a high proliferation rate and an easy access. Hence, we aimed to explore the effect of SHED on DN in Goto-Kakizaki (GK) rats. SHED were administered via the tail vein. Blood glucose, serum triglycerides and cholesterol, body weight, and urinary albumin were measured before and after administration. At 8 weeks after administration, real-time PCR, immunohistochemistry (IHC), and electron microscopy were employed to examine pathological changes in glomerular and tubulointerstitial tissue. Kidney weight and serum IL-1, IL-10, TNF-α, TGF-β, and HGF levels were measured. SHED engraftment in the kidneys was detected by transfecting green fluorescence protein (GFP). Type II epithelial-mesenchymal transition (EMT) in the tubule-interstitial and arteriolar regions has been reported to be an important pathological characteristic of DN. This study is the first to apply a transwell system for coculture to explore the effects of MSCs on the EMT of human proximal tubular epithelial (HK-2) cells. The effects of SHED on advanced glycation end product- (AGE-) activated EMT in HK-2 cells were explored by real-time PCR and western blot. At 8 weeks after administration, renal injury, including hyperglycemia, hyperlipidemia, increased urinary albumin excretion, ECM accumulation, and a fractional mesangial area, was dramatically attenuated. The serum levels of IL-1, TNF-α, and TGF-β were significantly downregulated, whereas the serum levels of IL-10 and HGF were upregulated by SHED. GFP expression confirmed the engraftment of SHED in diabetic kidneys. In addition, cocultured SHED inhibited AGE-induced EMT in HK-2 cells. In conclusion, SHED offer a novel potential effective therapeutic approach for ameliorating DN.http://dx.doi.org/10.1155/2019/2751475 |
| spellingShingle | Nanquan Rao Xiaotong Wang Jing Xie Jingzhi Li Yue Zhai Xiaoxia Li Tengjiaozi Fang Yuanyuan Wang Yuming Zhao Lihong Ge Stem Cells from Human Exfoliated Deciduous Teeth Ameliorate Diabetic Nephropathy In Vivo and In Vitro by Inhibiting Advanced Glycation End Product-Activated Epithelial-Mesenchymal Transition Stem Cells International |
| title | Stem Cells from Human Exfoliated Deciduous Teeth Ameliorate Diabetic Nephropathy In Vivo and In Vitro by Inhibiting Advanced Glycation End Product-Activated Epithelial-Mesenchymal Transition |
| title_full | Stem Cells from Human Exfoliated Deciduous Teeth Ameliorate Diabetic Nephropathy In Vivo and In Vitro by Inhibiting Advanced Glycation End Product-Activated Epithelial-Mesenchymal Transition |
| title_fullStr | Stem Cells from Human Exfoliated Deciduous Teeth Ameliorate Diabetic Nephropathy In Vivo and In Vitro by Inhibiting Advanced Glycation End Product-Activated Epithelial-Mesenchymal Transition |
| title_full_unstemmed | Stem Cells from Human Exfoliated Deciduous Teeth Ameliorate Diabetic Nephropathy In Vivo and In Vitro by Inhibiting Advanced Glycation End Product-Activated Epithelial-Mesenchymal Transition |
| title_short | Stem Cells from Human Exfoliated Deciduous Teeth Ameliorate Diabetic Nephropathy In Vivo and In Vitro by Inhibiting Advanced Glycation End Product-Activated Epithelial-Mesenchymal Transition |
| title_sort | stem cells from human exfoliated deciduous teeth ameliorate diabetic nephropathy in vivo and in vitro by inhibiting advanced glycation end product activated epithelial mesenchymal transition |
| url | http://dx.doi.org/10.1155/2019/2751475 |
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