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Modes of podocyte death in diabetic kidney disease: an update

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Abstract

Diabetic kidney disease (DKD) accounts for a large proportion of end-stage renal diseases that require renal replacement therapies including dialysis and transplantation. Therefore, it is critical to understand the occurrence and development of DKD. Podocytes are mainly injured during the development of DKD, ultimately leading to their extensive death and loss. In turn, the injury and death of glomerular podocytes are also the main culprits of DKD. This review introduces the characteristics of podocytes and summarizes the modes of their death in DKD, including apoptosis, autophagy, mitotic catastrophe (MC), anoikis, necroptosis, and pyroptosis. Apoptosis is characterized by nuclear condensation and the formation of apoptotic bodies, and it exerts a different effect from autophagy in mediating DKD-induced podocyte loss. MC mediates a faulty mitotic process while anoikis separates podocytes from the basement membrane. Moreover, pyroptosis activates inflammatory factors to aggravate podocyte injuries whilst necroptosis drives signaling cascades, such as receptor-interacting protein kinases 1 and 3 and mixed lineage kinase domain-like, ultimately promoting the death of podocytes. In conclusion, a thorough knowledge of the modes of podocyte death in DKD can help us understand the development of DKD and lay the foundation for strategies in DKD disease therapy.

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Abbreviations

AGEs:

Advanced glycation end products

Ang II:

Angiotensin II

AOPPs:

Advanced oxidation protein products

AMPK:

AMP -activated protein kinase

BASP1:

Brain acid-soluble protein 1

CB1R:

Cannabinoid receptor 1

Cdk5:

Cyclin-dependent kinase 5

CD2AP:

CD2-associated protein

DKD:

Diabetic kidney disease

EMT:

Epithelial-mesenchymal transformation

ERS:

Endoplasmic reticulum stress

EVs:

Extracellular vesicles

FOXO4:

Forkhead box O4

FSGS:

Focal segmental glomerulosclerosis

FSP1:

Fibroblast-specific protein 1

GBM:

Glomerular basement membrane

GSDMD:

Gasdermin D

GSK3β:

Glycogen synthase kinase-3β

HG:

High glucose

LN:

Lupus nephritis

LRP6:

Lipoprotein receptor-related protein 6

MAD:

Mitotic arrest deficiency

MC:

Mitotic catastrophe

MCNS:

Minimal change nephrotic syndrome

MDM2:

Murine double minute 2

miRNAs:

MicroRNAs

MLKL:

Mixed lineage kinase domain-like

mTOR:

Mammalian target of rapamycin

NLRP3:

Nucleotide-oligomerization domain-like receptor 3

PPARγ:

Peroxisome proliferator-activated receptor gamma

PI3-K:

Phosphoinositide 3-kinase

RAGE:

Receptors for AGEs

RARRES1:

Retinoic acid receptor responder protein 1

RIPK1:

Receptor-interacting protein kinase 1

ROS:

Reactive oxygen species

RIOK1:

RIO kinase 1

TGF-β:

Transforming growth factor-β

VEGF:

Vascular endothelial growth factor

Wnt:

Wingless‐type

WT1:

Wilms' tumor 1 transcription factor

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Acknowledgements

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Funding

This study was financially supported by the National Natural Science Foundation of China grants (81770711, 81873602, 81800610, 81974096, 81961138007, 81974097, 81900629, 82000664, 82170773, 82100794, 82100729).

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  1. Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang avenue number 1277, Wuhan, 430022, China

    Anni Jiang, Anni Song & Chun Zhang

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  1. Anni Jiang
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  2. Anni Song
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CZ conceptualized the review. AJ wrote a draft of the review. CZ and AS revised the paper. The figures were drawn by AJ. CZ performed the final edits.

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Correspondence to Chun Zhang.

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Jiang, A., Song, A. & Zhang, C. Modes of podocyte death in diabetic kidney disease: an update. J Nephrol 35, 1571–1584 (2022). https://doi.org/10.1007/s40620-022-01269-1

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