Evidence map›Paper›PMID 35013155›Full record

ArticleCell death & disease2022

PGC-1α inhibits the NLRP3 inflammasome via preserving mitochondrial viability to protect kidney fibrosis.

Bo Young Nam, Jong Hyun Jhee, Jimin Park, Seonghun Kim, Gyuri Kim, Jung Tak Park, Tae-Hyun Yoo, Shin-Wook Kang, Je-Wook Yu, Seung Hyeok Han

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
6.4field-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

50 citing papers in PubMed, 78 citations in OpenAlex.

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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

10 authors at 1 institution in 1 country.

Bo Young Nam *Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea.
Jong Hyun Jhee *Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Jimin ParkDepartment of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea.
Seonghun KimOral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea.ORCID http://orcid.org/0000-0003-3338-1156
Gyuri KimDepartment of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea.
Jung Tak ParkDepartment of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea.ORCID http://orcid.org/0000-0002-2325-8982
Tae-Hyun YooDepartment of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea.
Shin-Wook KangDepartment of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea.
Je-Wook YuDepartment of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Seung Hyeok HanDepartment of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea. hansh@yuhs.ac.ORCID http://orcid.org/0000-0001-7923-5635
Yonsei University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The NLRP3 inflammasome is activated by mitochondrial damage and contributes to kidney fibrosis. However, it is unknown whether PGC-1α, a key mitochondrial biogenesis regulator, modulates NLRP3 inflammasome in kidney injury. Primary renal tubular epithelial cells (RTECs) were isolated from C57BL/6 mice. The NLRP3 inflammasome, mitochondrial dynamics and morphology, oxidative stress, and cell injury markers were examined in RTECs treated by TGF-β1 with or without Ppargc1a plasmid, PGC-1α activator (metformin), and siPGC-1α. In vivo, adenine-fed and unilateral ureteral obstruction (UUO) mice were treated with metformin. In vitro, TGF-β1 treatment to RTECs suppressed the expressions of PGC-1α and mitochondrial dynamic-related genes. The NLRP3 inflammasome was also activated and the expression of fibrotic and cell injury markers was increased. PGC-1α induction with the plasmid and metformin improved mitochondrial dynamics and morphology and attenuated the NLRP3 inflammasome and cell injury. The opposite changes were observed by siPGC-1α. The oxidative stress levels, which are inducers of the NLRP3 inflammasome, were increased and the expression of TNFAIP3, a negative regulator of NLRP3 inflammasome regulated by PGC-1α, was decreased by TGF-β1 and siPGC-1α. However, PGC-1α restoration reversed these alterations. In vivo, adenine-fed and UUO mice models showed suppression of PGC-1α and TNFAIP3 and dysregulated mitochondrial dynamics. Moreover, the activation of oxidative stress and NLRP3 inflammasome, and kidney fibrosis were increased in these mice. However, these changes were significantly reversed by metformin. This study demonstrated that kidney injury was ameliorated by PGC-1α-induced inactivation of the NLRP3 inflammasome via modulation of mitochondrial viability and dynamics.

Indexed as

AnimalsFibrosisInflammasomesKidneyMiceMitochondriaMitochondrial DynamicsNLR Family, Pyrin Domain-Containing 3 ProteinOxidative StressPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaProtective AgentsSignal TransductionTransforming Growth Factor beta1Tumor Necrosis Factor alpha-Induced Protein 3Ureteral ObstructionInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mouseProtective AgentsTnfaip3 protein, mouseTransforming Growth Factor beta1Tumor Necrosis Factor alpha-Induced Protein 3

Identifiers

PMID35013155
PMCPMC8748677
OpenAlexW3116321057

What Socratic 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 Socratic graph.