Evidence map›Paper›PMID 35925422›Full record

ArticleClinical and experimental nephrology2022

Activation of necroptosis pathway in podocyte contributes to the pathogenesis of focal segmental glomerular sclerosis.

Haoqiang Hu, Mengyuan Li, Binfeng Chen, Chaohuan Guo, Niansheng Yang

Abstract read
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In one paragraph

Article in Clinical and experimental nephrology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Damage-Associated Molecular Patterns and Pattern Recognition Receptors in the Podocyte.Journal of the American Society of Nephrology : JASN · 2025
    Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Haoqiang Hu *Department of Nephrology, Affiliated Dongguan People's Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523000, China.
Mengyuan Li *Department of Rheumatology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China.
Binfeng ChenDepartment of Rheumatology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China.
Chaohuan GuoDepartment of Rheumatology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China.
Niansheng YangDepartment of Rheumatology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China. yangnsh@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0003-2624-5658
Sun Yat-sen University · CN

Funding

Dongguan Science and Technology of Social Development Program 201950715001183
6 · The paper itself

Abstract

backgroundFocal segmental glomerulosclerosis (FSGS) is characterized by podocyte damage and severe proteinuria. The exact mechanism of podocyte damage and loss remains unclear. Necroptosis, a lytic form of programmed cell death mediated by RIP3 and MLKL, has emerged as an important cell death pattern in multiple tissues and cell types. Necroptosis in FSGS has not been investigated.

methodsPublic GEO data regarding podocyte treated with vehicle or adriamycin (ADR) was identified and analyzed. Cultured human podocytes were used to explore the activation of necroptosis upon ADR stimulation. The expression of necroptosis pathway molecules, p-RIP3 and p-MLKL, was examined in the glomeruli and defoliated urinary podocytes of patients with FSGS. The effect of necroptosis inhibition was assessed in ADR-induced glomerulopathy mice using GSK872.

resultsPublicly available RNA-sequencing data analysis showed that both necroptosis and NLRP3 inflammasome pathway were up-regulated in ADR-injured podocyte. Immunofluorescent staining showed increased expression of p-RIP3 and p-MLKL, the active forms of RIP3 and MLKL, in podocytes of FSGS patients and ADR-induced glomerulopathy mice but not in the normal control. GSK872, an RIP3 kinase inhibitor, significantly inhibited the expression of p-RIP3, p-MLKL and activation of NLRP3 in cultured podocytes treated with ADR. GSK872 treatment of mice with ADR-induced nephropathy resulted in the reduced expression of p-RIP3, p-MLKL, NLRP3 and caspase-1 p20. GSK872 also significantly inhibited the expression of p-MLKL in the podocytes of ADR-induced nephropathy, resulting in the attenuation of proteinuria and renal histological lesions.

conclusionNecroptosis pathway might be a valuable target for the treatment of FSGS.

Indexed as

Glomerulosclerosis, Focal SegmentalKidney DiseasesPodocytesAnimalsCaspasesDoxorubicinHumansInflammasomesMiceNecroptosisNLR Family, Pyrin Domain-Containing 3 ProteinProteinuriaRNASclerosisCaspasesDoxorubicinInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinRNAFocal segmental glomerular sclerosisInflammasomeNecroptosisPodocyte

Identifiers

PMID35925422
OpenAlexW4289745159

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.