Evidence map›Paper›PMID 34369274›Full record

ArticleBioengineered2021

Transferrin receptor-mediated reactive oxygen species promotes ferroptosis of KGN cells via regulating NADPH oxidase 1/PTEN induced kinase 1/acyl-CoA synthetase long chain family member 4 signaling.

Lingzhi Zhang, Fang Wang, Dongmei Li, Yufeng Yan, Hongyan Wang

Open access · goldAbstract read
In one paragraph

Article in Bioengineered, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
6.6field-weighted citation impact, top 2% 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

64 citing papers in PubMed, 110 citations in OpenAlex.

  1. Review
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  11. Functional and Structural Uterine Changes in PCOS.International journal of molecular sciences · 2025
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Targeting ferroptosis for the treatment of female reproductive system disorders.Journal of molecular medicine (Berlin, Germany) · 2025
    Review
  17. Review
  18. Article
  19. Article
  20. Article

4 more citing papers are in PubMed but not listed here.

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.

Lingzhi ZhangDepartment of Obstetrics and Gynecology, Cao County People's Hospital, Shandong, China.
Fang WangDepartment of Obstetrics and Gynecology, Cao County People's Hospital, Shandong, China.
Dongmei LiDepartment of Obstetrics and Gynecology, Cao County People's Hospital, Shandong, China.
Yufeng YanDepartment of Obstetrics and Gynecology, Cao County People's Hospital, Shandong, China.
Hongyan WangDepartment of Obstetrics and Gynecology, Cao County People's Hospital, Shandong, China.
Jingning County People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Abnormal ovarian folliculogenesis is the main factor responsible for PCOS. Iron metabolism plays a vital role in endocrine disorder. This study aimed to investigate the potentials of iron metabolism in PCOS and the underlying molecular mechanisms. Mice were injected with dehydroepiandrosterone (DHEA) to establish the PCOS model in-vivo. H & E staining was performed for histological analysis; qRT-PCR and western blot were employed to determine the mRNA and protein expressions. Immunofluorescence was used for mitochondrial staining. Cellular functions were detected using CCK-8 and PI staining assays. Ferric ammonium citrate (FAC) activates the transferrin receptor (TFRC), increases the iron content, and suppresses the cell viability of the human granulosa-like tumor cell line (KGN). However, TFRC knockdown suppressed ferroptosis of KGN cells. Iron uptake mediated the activation of NADPH oxidase 1 (NOX1) signaling, which induced the release of reactive oxygen species (ROS) and mitochondrial damage. Moreover, TFRC activated PTEN induced kinase 1 (PINK1) signaling and induced mitophagy; iron-uptake-induced upregulation of acyl-CoA synthetase long chain family member 4 (ACSL4) was required for mitophagy activation and glutathione peroxidase 4 (GPX4) degradation. Additionally, FAC increased iron uptake and suppressed the folliculogenesis in-vivo. In conclusion, TFRC increased the iron content, mediated the release of ROS, activated mitophagy, and induced lipid peroxidation, which further promoted the ferroptosis of KGN cells. Therefore, the inhibitory effects of TFRC/NOX1/PINK1/ACSL4 signaling on folliculogenesis can be a potential target for PCOS.[Figure: see text].

Indexed as

AnimalsAntigens, CDCell LineCoenzyme A LigasesDisease Models, AnimalFemaleFerroptosisHumansIronLong-Chain-Fatty-Acid-CoA LigaseMiceMice, Inbred C57BLMitophagyNADPH Oxidase 1OvaryPolycystic Ovary SyndromeAntigens, CDCD71 antigenCoenzyme A LigasesIronLong-Chain-Fatty-Acid-CoA LigaseNADPH Oxidase 1NOX1 protein, humanProtein KinasesPTEN-Induced Putative KinasePTEN PhosphohydrolasePTEN protein, humanReactive Oxygen SpeciesReceptors, Transferrinferroptosisiron metabolismmitophagyPolycystic ovary syndrome

Identifiers

PMID34369274
PMCPMC8806504
OpenAlexW3188615224

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.