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The role of extracellular vesicles in podocyte autophagy in kidney disease

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Podocytes are the key cells involved in protein filtration in the glomerulus. Once proteins appear in the urine when podocytes fail, patients will end with renal failure due to the progression of glomerular damage if no proper treatment is applied. The injury and loss of podocytes can be attributed to diverse factors, such as genetic, immunologic, toxic, or metabolic disorders. Recently, autophagy has emerged as a key mechanism to eliminate the unwanted cytoplasmic materials and to prolong the lifespan of podocytes by alleviating cell damage and stress. Typically, the fundamental function of extracellular vesicles (EVs) is to mediate the intercellular communication. Recent studies have suggested that, EVs, especially exosomes, play a certain role in information transfer by communicating proteins, mRNAs, and microRNAs with recipient cells. Under physiological and pathological conditions, EVs assist in the bioinformation interchange between kidneys and other organs. It is suggested that EVs are related to the pathogenesis of acute kidney injury and chronic kidney disease, including glomerular disease, diabetic nephropathy, renal fibrosis and end-stage renal disease. However, the role of EVs in podocyte autophagy remains unclear so far. Here, this study integrated the existing information about the relevancy, diagnostic value and therapeutic potential of EVs in a variety of podocytes-related diseases. The accumulating evidence highlighted that autophagy played a critical role in the homeostasis of podocytes in glomerular disease.

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Abbreviations

ADSCs:

Adipose-derived stem cells.

AKI:

Acute kidney injury

AMPK:

AMP-activated protein kinase

ATF:

Activating transcription factor

ATG:

Autophagy-related gene

BMP:

Bone morphogenetic protein

BMSCs:

Bone marrow-derived mesenchymal stem cells

CHOP:

C/EBP homologous protein

CKD:

Chronic kidney disease

DN:

Diabetic nephropathy

EMT:

Epithelial–mesenchymal transition

ERS:

Endoplasmic reticulum stress

EVs:

Extracellular vesicles

ESRD:

End-stage renal disease

FSGS:

Focal segmental glomerulosclerosis

GBM:

Glomerular basement membrane

HG:

High glucose

HIF1:

Hypoxia-inducible factor 1

IRE1:

Inositol requiring enzyme 1

I/R:

Ischemia-reperfusion

JNK1:

c-junk N-terminal kinase 1

LC3:

Microtubule-associated protein light chain 3

LKB1:

Liver kinase B1

MCD:

Minimal change disease

MN:

Membranous nephropathy

mTORC:

Mammalian target of rapamycin complex

MVBs:

Multivesicular bodies

MPs:

Microparticles

NAFLD:

Non-alcoholic fatty liver disease

NLRP3:

Nucleotide-oligomerization domain-like receptor 3

NS:

Nephrotic syndrome

PERK:

Protein kinase RNA-like ER kinase

RAPTOR:

Regulatory associated protein of mTOR

Rheb:

Ras homolog enriched in brain

ROS:

Reactive oxygen species

SIRT1:

Sirtuin 1

SSNS:

Steroid-sensitive nephrotic syndrome

TSC1/2:

Tuberous sclerosis complex 1/2

ULK1:

Unc-51-like1

UPR:

Unfolded protein response

USCs:

Urine-derived stem cells

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Acknowledgements

BCS thank Prof. Qingshan Ma, Prof. Ping Luo and Prof. Kaishu Zhao for their constant encouragement, suggestions and support throughout.

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Authors and Affiliations

  1. Department of Nephrology, The Second Hospital of Jilin University, 218 ZiQiang Street, Changchun, 130041, Jilin, People’s Republic of China

    Baichao Sun & Guangdong Sun

  2. Department of Pediatric Nephrology, The First Hospital of Jilin University, Changchun, 130021, Jilin, People’s Republic of China

    Baichao Sun, Shubo Zhai & Li Zhang

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  1. Baichao Sun
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  2. Shubo Zhai
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  3. Li Zhang
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  4. Guangdong Sun
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BCS contributed in conceptualization and wrote the manuscript. SBZ and LZ equally contributed in reviewed the draft and made critical modifications. GDS was in charge of writing, and editing the manuscript. All authors had read and approved the final manuscript.

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Correspondence to Guangdong Sun.

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Sun, B., Zhai, S., Zhang, L. et al. The role of extracellular vesicles in podocyte autophagy in kidney disease. J. Cell Commun. Signal. 15, 299–316 (2021). https://doi.org/10.1007/s12079-020-00594-z

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