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Basic Sciences Investigations

Placenta-derived mesenchymal stem cells protect against diabetic kidney disease by upregulating autophagy-mediated SIRT1/FOXO1 pathway

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Article: 2303396 | Received 30 Aug 2023, Accepted 05 Jan 2024, Published online: 17 Jan 2024

Figures & data

Figure 1. Effects of placenta-derived mesenchymal stem cells (P-MSCs) on blood glucose (BG), lipid, renal function, and renal pathological structure in diabetic rats. A: Effect of P-MSCs on BG in diabetic kidney disease (DKD) rats; B: Effect of P-MSCs on triglyceride (TG) in DKD rats; C: Effect of P-MSCs on low-density lipoprotein cholesterol (LDL-C) in DKD rats; D: Effect of P-MSCs on blood urea nitrogen (BUN) in DKD rats; E: Effect of P-MSCs on urinary albumin-to-creatinine ratio (UACR) in DKD rats; F: Effect of P-MSCs on renal tubule and glomerulus in DKD rats; G: Pathological score of renal tubular injury(there are 6 rats in each group, and 5 pathological pictures are randomly selected for each group, so there are 30 pictures in each group to analyze the pathological score.)(nsP >0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).

Figure 1. Effects of placenta-derived mesenchymal stem cells (P-MSCs) on blood glucose (BG), lipid, renal function, and renal pathological structure in diabetic rats. A: Effect of P-MSCs on BG in diabetic kidney disease (DKD) rats; B: Effect of P-MSCs on triglyceride (TG) in DKD rats; C: Effect of P-MSCs on low-density lipoprotein cholesterol (LDL-C) in DKD rats; D: Effect of P-MSCs on blood urea nitrogen (BUN) in DKD rats; E: Effect of P-MSCs on urinary albumin-to-creatinine ratio (UACR) in DKD rats; F: Effect of P-MSCs on renal tubule and glomerulus in DKD rats; G: Pathological score of renal tubular injury(there are 6 rats in each group, and 5 pathological pictures are randomly selected for each group, so there are 30 pictures in each group to analyze the pathological score.)(nsP >0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).

Figure 2. Effects of placenta-derived mesenchymal stem cells (P-MSCs) and 3-methyladenine (3-MA) on glomerular podocyte fissure membrane proteins podocin and nephrin in diabetic kidney disease (DKD) rats. A-B: Immunofluorescence was used to detect the expression of podocin in rat glomerulus. C-D: Effects of P-MSCs and 3-MA on nephrin in DKD rats. (****p < 0.0001).

Figure 2. Effects of placenta-derived mesenchymal stem cells (P-MSCs) and 3-methyladenine (3-MA) on glomerular podocyte fissure membrane proteins podocin and nephrin in diabetic kidney disease (DKD) rats. A-B: Immunofluorescence was used to detect the expression of podocin in rat glomerulus. C-D: Effects of P-MSCs and 3-MA on nephrin in DKD rats. (****p < 0.0001).

Figure 3. Effects of placenta-derived mesenchymal stem cells (P-MSCs) and 3-methyladenine (3-MA) on autophagy-related proteins, SITR1 and FOXO1 in renal tissue of diabetic kidney disease (DKD) rats. A: Expression of autophagy-related proteins Beclin1, LC3, SITR1, and FOXO1 was evaluated by immunohistochemical staining in renal tissue of rats in each group; B: Effects of P-MSCs and 3-MA on Beclin1 in renal tissue of DKD rats; C: Effects of P-MSCs and 3-MA on LC3 in renal tissue of DKD rats D: Effects of P-MSCs and 3-MA on SITR1 in renal tissue of DKD rats; E: Effects of P-MSCs and 3-MA on FOXO1 in renal tissue of DKD rats. (***p < 0.001,****p < 0.0001).

Figure 3. Effects of placenta-derived mesenchymal stem cells (P-MSCs) and 3-methyladenine (3-MA) on autophagy-related proteins, SITR1 and FOXO1 in renal tissue of diabetic kidney disease (DKD) rats. A: Expression of autophagy-related proteins Beclin1, LC3, SITR1, and FOXO1 was evaluated by immunohistochemical staining in renal tissue of rats in each group; B: Effects of P-MSCs and 3-MA on Beclin1 in renal tissue of DKD rats; C: Effects of P-MSCs and 3-MA on LC3 in renal tissue of DKD rats D: Effects of P-MSCs and 3-MA on SITR1 in renal tissue of DKD rats; E: Effects of P-MSCs and 3-MA on FOXO1 in renal tissue of DKD rats. (***p < 0.001,****p < 0.0001).

Figure 4. Effects of high glucose on podocyte- and autophagy-related proteins Beclin1 of podocytes. A-B: Immunofluorescence was used to detect the expression of podocin expression in podocytes with different concentrations of high glucose; C-D: Western blot was used to detect the effects of different concentrations of high glucose on podocyte autophagy. (*p < 0.05, **p < 0.01).

Figure 4. Effects of high glucose on podocyte- and autophagy-related proteins Beclin1 of podocytes. A-B: Immunofluorescence was used to detect the expression of podocin expression in podocytes with different concentrations of high glucose; C-D: Western blot was used to detect the effects of different concentrations of high glucose on podocyte autophagy. (*p < 0.05, **p < 0.01).

Figure 5. Effects of placenta-derived mesenchymal stem cells (P-MSCs) and 3-methyladenine (3-MA) on autophagy-related proteins and SIRT1, FOXO1 in high glucose-induced MPC5 cells A-B: Effects of P-MSCs on podocin and autophagy-related proteins (Beclin1 and LC3) in high glucose-induced MPC5; C-D: Western blot was used to detect the expression of SIRT1 and FOXO1 in high glucose-induced MPC5 cells treated with P-MSCs; E: PCR was used to evaluate SIRT1 mRNA expression in high glucose-induced MPC5 cells by P-MSCs; F-G: Effects of P-MSCs and 3-MA on podocin in high glucose-induced MPC5 cells. (**p < 0.01, ***p < 0.001, ****p < 0.000, ## p < 0.001).

Figure 5. Effects of placenta-derived mesenchymal stem cells (P-MSCs) and 3-methyladenine (3-MA) on autophagy-related proteins and SIRT1, FOXO1 in high glucose-induced MPC5 cells A-B: Effects of P-MSCs on podocin and autophagy-related proteins (Beclin1 and LC3) in high glucose-induced MPC5; C-D: Western blot was used to detect the expression of SIRT1 and FOXO1 in high glucose-induced MPC5 cells treated with P-MSCs; E: PCR was used to evaluate SIRT1 mRNA expression in high glucose-induced MPC5 cells by P-MSCs; F-G: Effects of P-MSCs and 3-MA on podocin in high glucose-induced MPC5 cells. (**p < 0.01, ***p < 0.001, ****p < 0.000, ## p < 0.001).

Figure 6. Effects of SIRT1 siRNA on SIRT1/FOXO1 and autophagy-related proteins in MPC5 cells treated with high glucose and placenta-derived mesenchymal stem cells (P-MSCs). A: SIRT1 siRNA inhibited P-MSCs from promoting SIRT1 mRNA expression in high glucose-induced MPC5 cells; B-C: Effects of SIRT1 siRNA on SIRT1 and FOXO1 expression in MPC5 cells treated with high glucose and P-MSCs; D-E: Effects of SIRT1 siRNA on podocin and autophagy-related proteins in MPC5 cells treated with high glucose and P-MSCs. (**p < 0.01).

Figure 6. Effects of SIRT1 siRNA on SIRT1/FOXO1 and autophagy-related proteins in MPC5 cells treated with high glucose and placenta-derived mesenchymal stem cells (P-MSCs). A: SIRT1 siRNA inhibited P-MSCs from promoting SIRT1 mRNA expression in high glucose-induced MPC5 cells; B-C: Effects of SIRT1 siRNA on SIRT1 and FOXO1 expression in MPC5 cells treated with high glucose and P-MSCs; D-E: Effects of SIRT1 siRNA on podocin and autophagy-related proteins in MPC5 cells treated with high glucose and P-MSCs. (**p < 0.01).

Figure 7. Schematic diagram of the effects of P-MSCs on podocyte in DKD via enhancing SIRT1/FOXO1 pathway-mediated autophagy(visual abstract).

Figure 7. Schematic diagram of the effects of P-MSCs on podocyte in DKD via enhancing SIRT1/FOXO1 pathway-mediated autophagy(visual abstract).