Abstract
As a common clinical chronic disease, the incidence of diabetes is increasing year by year. According to the latest statistics from the International Diabetes Federation, as of 2019, the global prevalence of diabetes has reached 8.3%. This study aims to investigate the effect of CXCL-13 on the migration ability of human mesenchymal stem cells (hMSCs) and to clarify the specific molecular mechanism of the protective effect of hMSCs on islet B cells. The hMSCs were cultured in high-glucose environment, and the effect of CXCL-13 on the migration ability of hMSCs was determined by Transwell experiment. After coculture of hMSCs and islet B cells, the activity of cells was detected by CCK8 assay, the expression of Ki-67 in cells was detected by RT-PCR, and the expression of P53 was detected by Western blot to investigate the effect of hMSCs on the proliferation and apoptosis of islet B cells. The effect of hMSCs on the function of islet B cells was determined by glucose stimulated insulin secretion experiment. Transwell experiment results showed that CXCL-13 could promote the migration of hMSCs to islet B cells in high-glucose environment. The results of CCK-8 showed that the cell activity in the coculture group was significantly higher than that of the other groups, and RT-PCR showed that the expression of Ki-67 was significantly increased in the coculture group of hMSCs and islet B cells. The results of Western blot showed that the expression of P53 was significantly decreased in the coculture group, and the glucose stimulated insulin secretion test showed that insulin secretion was significantly increased. It was found that after the inhibition of ATK, cell activity was significantly reduced, and apoptosis was significantly increased. Meanwhile, the expression of Ki-67 was inhibited, the expression of P-53 was significantly increased, and insulin secretion was significantly reduced. To sum up, in a high-glucose environment, CXCL-13 effectively promoted the migration of hMSCs, and hMSCs protected the activity and function of islet B cells through Akt signaling pathway.
Highlights
IntroductionIn 2019, the number of diabetic patients in China has reached 116 million, the largest diabetic patient number in the world, and about 90% of them are type 2 diabetes patients [1]. e mechanism of the development of type 2 diabetes is that long-term chronic hyperglycemia significantly inhibits the activity of islet B cells and promotes the apoptosis of islet B cells [2, 3]. e decrease in islet B cells number leads to decreased function of islet B cells [4].erefore, the effective protection of the activity of isletB cells in high-glucose environment has become a new target for the treatment of type 2 diabetes. [5]As seed cells, stem cells are expected to be used in the treatment of a variety of diseases due to their self-renewal and multidirectional differentiation abilities [6]
Mesenchymal stem cells and islet B cells were cultured in a high-glucose environment, and CXCL-13 was added into the culture medium to clarify the effect of CXCL-13 on the migration ability of mesenchymal stem cells in a high-glucose environment. e specific mechanism of the protective effect of mesenchymal stem cells on islet B cells was explored by adding AKT pathway inhibitors into the culture medium. e results of our study showed that CXCL-13 could effectively promote the migration and aggregation of hMSCs to islet B cells in high-glucose culture environment
Experiment grouping was as follows. e hMSCs group normally cultured was taken as the control group, the group with 80 ummol/L CXCL-13 stimulant was taken as the CXCL-13 control group, the hMSCs cultured in high-glucose environment was taken as the cultured group in high-glucose environment, and the group cultured with 80 ummol/L CXCL-13 stimulant was taken as the stimulated group in high-glucose environment
Summary
In 2019, the number of diabetic patients in China has reached 116 million, the largest diabetic patient number in the world, and about 90% of them are type 2 diabetes patients [1]. e mechanism of the development of type 2 diabetes is that long-term chronic hyperglycemia significantly inhibits the activity of islet B cells and promotes the apoptosis of islet B cells [2, 3]. e decrease in islet B cells number leads to decreased function of islet B cells [4].erefore, the effective protection of the activity of isletB cells in high-glucose environment has become a new target for the treatment of type 2 diabetes. [5]As seed cells, stem cells are expected to be used in the treatment of a variety of diseases due to their self-renewal and multidirectional differentiation abilities [6]. Erefore, mesenchymal stem cells are expected to be an adequate tool in the effective treatment of type 2 diabetes. Liu et al [9] injected mesenchymal stem cells into patients with type 2 diabetes and found that fasting blood glucose was significantly reduced after stem cell inhibition. Ese studies proved that mesenchymal stem cells have good effect on the treatment of type 2 diabetes. Studies have shown that high-glucose environment could inhibit the expression of Ki67 in cells. As a protein related to cell proliferation, the inhibition of Ki67 proves that high-glucose environment may have a certain negative effect on cell proliferation [10]. Previous studies have shown that mesenchymal stem cells could significantly inhibit the expression of P53 in fibroblasts in high-glucose environment. As a protein related to cell aging, the inhibition of P53 expression proved that stem cells could inhibit cell aging in high-glucose environment [11, 12]
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