Evidence map›Paper›PMID 34867948›Full record

ArticleFrontiers in immunology2021

Novel Effects of Combination Therapy Through Inhibition of Caspase-1/Gasdermin D Induced-Pyroptosis in Lupus Nephritis.

Heng Cao, Junyu Liang, Jing Liu, Ye He, Yini Ke, Yiduo Sun, Song Jiang, Jin Lin

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 6% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
  2. Observational
  3. Review
  4. Article
  5. Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026
    Review
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  17. Article
  18. Role of gasdermins in chronic kidney disease.Frontiers in immunology · 2025
    Review
  19. Article
  20. 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

8 authors at 2 institutions in 1 country.

Heng CaoDepartment of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Junyu LiangDepartment of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jing LiuNational Clinical Research Center of Kidney Diseases, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China.
Ye HeDepartment of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yini KeDepartment of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yiduo SunDepartment of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Song JiangNational Clinical Research Center of Kidney Diseases, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China.
Jin LinDepartment of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
First Affiliated Hospital Zhejiang University · CNNanjing Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objectives: Combination therapy with mycophenolate mofetil, tacrolimus and steroids are effective in achieving complete remission in lupus nephritis (LN). Combination therapy uniquely downregulated caspase-1 compared with monotherapies, which can cleave gasdermin D (GSDMD) and was recently identified as the pyroptosis executioner. We therefore investigated whether combination therapy enabled the suppression of caspase-1/GSDMD-mediated pyroptosis in LN. Methods: Expression and activation of GSDMD were detected in kidney specimens of the human and mouse with LN using immunohistochemical staining and immunoblotting. Primary podocytes isolated from MRL/lpr mice were incubated with LPS+ATP, and pretreated with monotherapy or combination therapy. Inhibition of caspase-1/GSDMD-induced pyroptosis by combination therapy were assessed in MRL/lpr mice and human specimens. Pyroptosis was examined using a FAM caspase-1 kit and flow cytometry. The correlation between pyroptosis in peripheral blood and the systemic lupus erythematosus disease activity index (SLEDAI) was analyzed. Results: Kidney tissue specimens from LN patients and mice exhibited greatly increased expression levels and cleavage of GSDMD. In cultured podocytes, combination treatment significantly suppressed the activation of NLRP3 and caspase-1 and reduced GSDMD N-terminal levels. Combination therapy repressed disease progression through inhibition of caspase-1/GSDMD-mediated pyroptosis in both humans and MRL/lpr mice. Caspase-1/PI positive cell numbers in peripheral blood were positively correlated with SLE-DAI. LN patients with complete remission and partial remission had remarkably reduced caspase-1/PI positive cell numbers compared to baseline. Ac-FLTD-CMK, a GSDMD-derived inhibitor, prevented the development of LN. Conclusion: Combination therapy suppressed caspase-1/GSDMD-mediated pyroptosis

Indexed as

AdolescentAdultAgedAnimalsCalcineurin InhibitorsCaspase 1Caspase InhibitorsCells, CulturedCohort StudiesDisease Models, AnimalDrug Therapy, CombinationFemaleGasderminsHumansIntracellular Signaling Peptides and ProteinsKidneyCalcineurin InhibitorsCasp1 protein, mouseCaspase 1Caspase InhibitorsGasderminsGSDMD protein, humanGsdmd protein, mouseIntracellular Signaling Peptides and ProteinsMycophenolic AcidPhosphate-Binding ProteinsPrednisoneTacrolimuscaspase-1gasdermin Dlupus nephritispyroptosistherapy

Identifiers

PMID34867948
PMCPMC8639704
OpenAlexW3216766663

What OpenQuestion holds

Textmetadata
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.