Evidence map›Paper›PMID 40603451›Full record

ArticleScientific reports2025

Transcription factor EB improves hypoxic pulmonary hypertension in fetal rats by suppressing NLRP3 inflammasome activation via induction of mitophagy.

Chaohong Chen, Zaoye Xie, Dang Ao, Yinhui Chen, Ling Liu, Chengyan Li

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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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

6 authors.

Chaohong ChenDepartment of Pediatrics, Affiliated Hospital of Guangdong Medical University, No. 57, Renmin Avenue (South), Xiashan, Zhanjiang, 524000, Guangdong, People's Republic of China.
Zaoye XieDepartment of Pediatrics, Affiliated Hospital of Guangdong Medical University, No. 57, Renmin Avenue (South), Xiashan, Zhanjiang, 524000, Guangdong, People's Republic of China.
Dang AoDepartment of Pediatrics, Affiliated Hospital of Guangdong Medical University, No. 57, Renmin Avenue (South), Xiashan, Zhanjiang, 524000, Guangdong, People's Republic of China.
Yinhui ChenDepartment of Pediatrics, Affiliated Hospital of Guangdong Medical University, No. 57, Renmin Avenue (South), Xiashan, Zhanjiang, 524000, Guangdong, People's Republic of China.
Ling LiuDepartment of Pediatrics, Affiliated Hospital of Guangdong Medical University, No. 57, Renmin Avenue (South), Xiashan, Zhanjiang, 524000, Guangdong, People's Republic of China.
Chengyan LiDepartment of Pediatrics, Affiliated Hospital of Guangdong Medical University, No. 57, Renmin Avenue (South), Xiashan, Zhanjiang, 524000, Guangdong, People's Republic of China. chengyan_may@163.com.

Funding

Affiliated Hospital of Guangdong Medical University "Clinical Medicine plus" Scientific Research Cooperation Project; Affiliated Hospital of Guangdong Medical University Clinical Research Program LCYJ2020DL01Guangdong Medical Research Foundation A2020286Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases 2022B1212030003the high-level talents scientific research start-up funds of the Affiliated Hospital of Guangdong Medical University GCC2024024The science and technology project of Zhanjiang City 2022A01181
6 · The paper itself

Abstract

Persistent pulmonary hypertension of the newborn (PPHN) represents a life-threatening cardiopulmonary condition characterized by hypoxia-driven pulmonary vascular remodeling. While transcription factor EB (TFEB), a master regulator of cellular adaptation to hypoxia, has been implicated in vascular pathologies, its mechanistic role in PPHN remains undefined. This study elucidates the molecular interplay of TFEB in hypoxia-induced PPHN pathogenesis. Fetal rat models of hypoxia-induced PPHN, including untreated hypoxic models and hypoxic models treated with the TFEB inhibitor Eltrombopag (EO), as well as a hypoxia-induced human pulmonary artery endothelial cell (HPAEC) model, were established. Multimodal assessments, including histopathology, qRT-PCR, JC-1 staining, immunofluorescence, flow cytometry, and Western blotting, were employed to evaluate the effects of TFEB on mitophagy and NLRP3 inflammasome. In the hypoxia group, significant thickening of the pulmonary arterioles and right ventricular wall was observed. Immunostaining revealed a significant increase in the relative staining density of TFEB-positive, NLRP3-positive, and LC3-positive cells, alongside elevated expression of mitophagy-proteins and NLRP3 inflammasome-related proteins. TFEB inhibition downregulated the expression of PINK1, TOMM20, COX IV, P62, and LC3II/I ratio, impairing mitophagy, while upregulating eNOS, NLRP3, and GSDMD, thereby enhancing NLRP3 activation and pyroptosis. In the EO group, fetal rats exhibited more pronounced pulmonary arteriole thickening, intensified fluorescence signals for NLRP3, caspase-1, and GSDMD, reduced mitophagy-related protein expression, and further elevated NLRP3 inflammasome-related protein and GSDMD expression. TFEB exerts a protective effect in PPHN by inhibiting NLRP3 inflammasome activation through PINK1/Parkin-mediated mitophagy, highlighting TFEB's potential as a therapeutic target for hypoxia-induced PPHN.

Indexed as

Basic Helix-Loop-Helix Leucine Zipper Transcription FactorsHypertension, PulmonaryHypoxiaInflammasomesMitophagyNLR Family, Pyrin Domain-Containing 3 ProteinPersistent Fetal Circulation SyndromeAnimalsDisease Models, AnimalEndothelial CellsFemaleHumansPregnancyPulmonary ArteryRatsRats, Sprague-DawleyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratTFEB protein, ratHypoxic pulmonary hypertensionMitophagyNLRP3 inflammasomePINK1/ParkinTranscription factor EB

Identifiers

PMID40603451
PMCPMC12223042

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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.