CLC number:
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2024-07-17
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Hao ZHANG, Xinshu WANG, Bo HU, Peicheng LI, Yierfan ABUDUAINI, Hongmei ZHAO, Ayinaer JIEENSIHAN, Xishuang CHEN, Shiyu WANG, Nuojin GUO, Jian YUAN, Yunhui LI, Lei LI, Yuntong YANG, Zhongmin LIU, Zhaosheng TANG, Hua WANG. Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus[J]. Journal of Zhejiang University Science B, 2024, 25(7): 568-580.
@article{title="Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus",
author="Hao ZHANG, Xinshu WANG, Bo HU, Peicheng LI, Yierfan ABUDUAINI, Hongmei ZHAO, Ayinaer JIEENSIHAN, Xishuang CHEN, Shiyu WANG, Nuojin GUO, Jian YUAN, Yunhui LI, Lei LI, Yuntong YANG, Zhongmin LIU, Zhaosheng TANG, Hua WANG",
journal="Journal of Zhejiang University Science B",
volume="25",
number="7",
pages="568-580",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300182"
}
%0 Journal Article
%T Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus
%A Hao ZHANG
%A Xinshu WANG
%A Bo HU
%A Peicheng LI
%A Yierfan ABUDUAINI
%A Hongmei ZHAO
%A Ayinaer JIEENSIHAN
%A Xishuang CHEN
%A Shiyu WANG
%A Nuojin GUO
%A Jian YUAN
%A Yunhui LI
%A Lei LI
%A Yuntong YANG
%A Zhongmin LIU
%A Zhaosheng TANG
%A Hua WANG
%J Journal of Zhejiang University SCIENCE B
%V 25
%N 7
%P 568-580
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300182
TY - JOUR
T1 - Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus
A1 - Hao ZHANG
A1 - Xinshu WANG
A1 - Bo HU
A1 - Peicheng LI
A1 - Yierfan ABUDUAINI
A1 - Hongmei ZHAO
A1 - Ayinaer JIEENSIHAN
A1 - Xishuang CHEN
A1 - Shiyu WANG
A1 - Nuojin GUO
A1 - Jian YUAN
A1 - Yunhui LI
A1 - Lei LI
A1 - Yuntong YANG
A1 - Zhongmin LIU
A1 - Zhaosheng TANG
A1 - Hua WANG
J0 - Journal of Zhejiang University Science B
VL - 25
IS - 7
SP - 568
EP - 580
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300182
Abstract: diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red “O” staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.
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