Placental Mesenchymal Stem Cells Alleviate Podocyte Injury in Diabetic Kidney Disease by Modulating Mitophagy via the SIRT1-PGC-1alpha-TFAM Pathway
Abstract
:1. Introduction
2. Results
2.1. Podocyte Injury and PINK1/Parkin-Mediated Mitophagy Inhibition Induced by High Glucose in the Mouse Podocyte Cell Line
2.2. P-MSCs Attenuated HG-Induced Podocyte Injury and PINK1/Parkin-Mediated Mitophagy Inhibition
2.3. P-MSCs Extenuated HG-Mediated Mitochondrial Dysfunction and Reactive Oxygen Species Accumulation
2.4. P-MSCs Alleviated HG-Induced Podocyte Injury and PINK1/Parkin-Mediated Mitophagy Inhibition by Activating the SIRT1-PGC-1α-TFAM Signaling Pathway
2.5. P-MSCs Ameliorated Streptozotocin-Induced Podocyte Injury and PINK1/Parkin-Mediated Mitophagy in DKD Rats
3. Discussion
4. Materials and Methods
4.1. Reagents and Antibodies
4.2. Cell Culture
4.3. Transfections of Plasmids and Small Interfering RNAs
4.4. WB Assay
4.5. RT-PCR
4.6. Immunofluorescence
4.7. ΔΨm, ATP Content, and ROS Determination
4.8. Transmission Electron Microscopy
4.9. Experimental Animals
4.10. Immunohistochemistry
4.11. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
DKD | diabetic kidney disease |
MSCs | mesenchymal stem cells |
P-MSCs | placenta derived mesenchymal stem cells |
SIRT1 | silencing information regulator 2 related enzyme 1 |
PINK1 | phosphatase and tensin homolog–induced kinase |
PGC-1α | peroxisome proliferator-activated receptor γ coactivator-1alpha |
TFAM | transcription factor A, mitochondrial |
FBS | fetal bovine serum |
β-actin | beta actin |
HG | high glucose |
NC | negative control |
siRNAs | small interfering RNAs |
PBS | phosphate-buffered saline |
PBST | phosphate-buffered saline with Tween 20 |
WB | Western blot |
RT-PCR | reverse transcription–polymerase chain reaction |
ΔΨm | mitochondrial membrane potential |
ROS | reactive oxygen species |
STZ | streptozotocin |
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Han, X.; Wang, J.; Li, R.; Huang, M.; Yue, G.; Guan, L.; Deng, Y.; Cai, W.; Xu, J. Placental Mesenchymal Stem Cells Alleviate Podocyte Injury in Diabetic Kidney Disease by Modulating Mitophagy via the SIRT1-PGC-1alpha-TFAM Pathway. Int. J. Mol. Sci. 2023, 24, 4696. https://doi.org/10.3390/ijms24054696
Han X, Wang J, Li R, Huang M, Yue G, Guan L, Deng Y, Cai W, Xu J. Placental Mesenchymal Stem Cells Alleviate Podocyte Injury in Diabetic Kidney Disease by Modulating Mitophagy via the SIRT1-PGC-1alpha-TFAM Pathway. International Journal of Molecular Sciences. 2023; 24(5):4696. https://doi.org/10.3390/ijms24054696
Chicago/Turabian StyleHan, Xiudan, Jiao Wang, Ruilin Li, Meiling Huang, Guanru Yue, Lulu Guan, Yuanyuan Deng, Wei Cai, and Jixiong Xu. 2023. "Placental Mesenchymal Stem Cells Alleviate Podocyte Injury in Diabetic Kidney Disease by Modulating Mitophagy via the SIRT1-PGC-1alpha-TFAM Pathway" International Journal of Molecular Sciences 24, no. 5: 4696. https://doi.org/10.3390/ijms24054696