Dataset Information

Therapeutic Potential Targeting Podocyte Mitochondrial Dysfunction in Focal Segmental Glomerulosclerosis.

ABSTRACT:

Background

Podocytes are essential components of the glomerular filtration barrier and essential for the proper filtration function of the glomerulus. Podocyte injury under various stress conditions is the primary pathogenesis and key determinant of focal segmental glomerulosclerosis (FSGS) with prominent clinical manifestations of proteinuria or nephrotic syndrome.

Summary

Under physiological conditions, a highly coordinated mitochondrial quality control system, including antioxidant defenses, mitochondrial dynamics (fusion, fission, and mitophagy), and mitochondrial biogenesis, guarantees the sophisticated structure and various functions of podocytes. However, under FSGS pathological conditions, mitochondria encounter oxidative stress, dynamics disturbances, and defective mitochondrial biogenesis. Moreover, mutations in mitochondrial DNA and mitochondria-related genes are also strongly associated with FSGS. Based on these pieces of evidence, bioactive agents that function to relieve mitochondrial oxidative stress and promote mitochondrial biogenesis have been proven effective in preclinical FSGS models. Targeting the mitochondrial network is expected to provide new therapeutic strategies for the treatment of FSGS and delay its progression to end-stage renal disease.

Key messages

Mitochondrial dysfunction plays a key role in podocyte injury and FSGS progression. This review summarized recent advances in the study of mitochondrial homeostatic imbalance and dysfunction in FSGS and discussed the potential of mitochondria-targeted therapeutics in improving FSGS and retarding its progression to end-stage renal disease.

SUBMITTER: Li Y

PROVIDER: S-EPMC10601935 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Therapeutic Potential Targeting Podocyte Mitochondrial Dysfunction in Focal Segmental Glomerulosclerosis.

Li Yuting Y Fan Jiaojiao J Zhu Wenping W Niu Yujia Y Wu Mengqiu M Zhang Aihua A

Kidney diseases (Basel, Switzerland) 20230328 4

<h4>Background</h4>Podocytes are essential components of the glomerular filtration barrier and essential for the proper filtration function of the glomerulus. Podocyte injury under various stress conditions is the primary pathogenesis and key determinant of focal segmental glomerulosclerosis (FSGS) with prominent clinical manifestations of proteinuria or nephrotic syndrome.<h4>Summary</h4>Under physiological conditions, a highly coordinated mitochondrial quality control system, including antioxi ...[more]

PMID: 37900001

Similar Datasets

Project description:Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant-important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele-associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g, glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g, to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.

Dataset Information

Therapeutic Potential Targeting Podocyte Mitochondrial Dysfunction in Focal Segmental Glomerulosclerosis.

Background

Summary

Key messages

Publications

Therapeutic Potential Targeting Podocyte Mitochondrial Dysfunction in Focal Segmental Glomerulosclerosis.

Similar Datasets

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