Evidence map›Paper›PMID 34511597›Full record

ArticleCell death & disease2021

Liproxstatin-1 attenuates unilateral ureteral obstruction-induced renal fibrosis by inhibiting renal tubular epithelial cells ferroptosis.

Bo Zhang, Xiang Chen, Feng Ru, Yu Gan, Bingsheng Li, Weiping Xia, Guoyu Dai, Yao He, Zhi Chen

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
18.8field-weighted citation impact, top 1% 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

113 citing papers in PubMed, 205 citations in OpenAlex.

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  18. Advances in the Targeted Drug Delivery System for Renal Fibrosis.International journal of nanomedicine · 2026
    Review
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  20. Article

53 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

9 authors at 1 institution in 1 country.

Bo ZhangDepartment of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Xiang ChenDepartment of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.ORCID 0000-0003-0688-636X
Feng RuDepartment of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Yu GanDepartment of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Bingsheng LiDepartment of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Weiping XiaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Guoyu DaiDepartment of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Yao He *Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. heyao1984@163.com.ORCID 0000-0003-0045-3192
Zhi Chen *Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. czhi1011@126.com.ORCID 0000-0003-0175-4907
Central South University · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81770693
6 · The paper itself

Abstract

Renal fibrosis is a common pathological process that occurs with diverse etiologies in chronic kidney disease. However, its regulatory mechanisms have not yet been fully elucidated. Ferroptosis is a form of non-apoptotic regulated cell death driven by iron-dependent lipid peroxidation. It is currently unknown whether ferroptosis is initiated during unilateral ureteral obstruction (UUO)-induced renal fibrosis and its role has not been determined. In this study, we demonstrated that ureteral obstruction induced ferroptosis in renal tubular epithelial cells (TECs) in vivo. The ferroptosis inhibitor liproxstatin-1 (Lip-1) reduced iron deposition, cell death, lipid peroxidation, and inhibited the downregulation of GPX4 expression induced by UUO, ultimately inhibiting ferroptosis in TECs. We found that Lip-1 significantly attenuated UUO-induced morphological and pathological changes and collagen deposition of renal fibrosis in mice. In addition, Lip-1 attenuated the expression of profibrotic factors in the UUO model. In vitro, we used RSL3 treatment and knocked down of GPX4 level by RNAi in HK2 cells to induce ferroptosis. Our results indicated HK2 cells secreted various profibrotic factors during ferroptosis. Lip-1 was able to inhibit ferroptosis and thereby inhibit the secretion of the profibrotic factors during the process. Incubation of kidney fibroblasts with culture medium from RSL3-induced HK2 cells promoted fibroblast proliferation and activation, whereas Lip-1 impeded the profibrotic effects. Our study found that Lip-1 may relieve renal fibrosis by inhibiting ferroptosis in TECs. Mechanistically, Lip-1 could reduce the activation of surrounding fibroblasts by inhibiting the paracrine of profibrotic factors in HK2 cells. Lip-1 may potentially be used as a therapeutic approach for the treatment of UUO-induced renal fibrosis.

Indexed as

FerroptosisAnimalsCarbolinesCell DeathCell LineCell ProliferationCell ShapeCollagenDisease Models, AnimalEpithelial CellsFibrosisHumansIronKidney TubulesLipid PeroxidationMaleCarbolinesCollagenglutathione peroxidase 4, mouseIronliproxstatin-1Phospholipid Hydroperoxide Glutathione PeroxidaseQuinoxalinesRSL3 compoundSpiro Compounds

Identifiers

PMID34511597
PMCPMC8435531
OpenAlexW3199602330

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.