Evidence map›Paper›PMID 42168992›Full record

ArticleJournal of nanobiotechnology2026

Mycobacterium tuberculosis-induced PCBP1 degradation drives macrophage ferroptosis to promote infection: a lung-macrophage-targeted RNAa nanotherapy.

Huan-Shao Huang, Jia-Xin Chi, Jia-Jun Wang, Le-Yao Xiao, Lan Chen, Shi-Ying Lai, Wan-Yi Liu, Feng Yang, Kang-Sheng Liao, Jiang Pi and 3 more

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

The trial behind it

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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

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0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Huan-Shao Huang *Dongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China.
Jia-Xin Chi *Dongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China.
Jia-Jun Wang *Dongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China.
Le-Yao XiaoDongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China.
Lan ChenDongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China.
Shi-Ying LaiDongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China.
Wan-Yi LiuDongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China.
Feng YangDongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China.
Kang-Sheng LiaoDongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China.
Jiang PiDongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China.
Yan-Guang CongDongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China. ygcong@hotmail.com.
Yi-Ming ShaoDongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China. sym@gdmu.edu.cn.
Jun-Fa XuDongguan Key Laboratory for Pathogenesis and Experimental Diagnosis of Infectious Diseases, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, 523710, Guangdong province, China. xujunfa@gdmu.edu.cn.

Funding

Discipline construction project of Guangdong Medical University No. 4SG23030G, 4SG24025G, 4SG24044G, 4SG24129G, 4SG23143G and 4SG23077GDongguan Science and Technology of Social Development Program No. 20211800905072Guangdong Basic and Applied Basic Research Foundation No. 2022A1515010525Guangdong Basic and Applied Basic Research Foundation No. 2023A1515140177Guangdong Medical Scientific Research Found No. A2024616Innovation Team Project of Universities in Guangdong Province No. 2022KCXTD010National Natural Science Foundation of China No. 82072151National Natural Science Foundation of China No. 82270013, 81870016Project of Songshan Lake Innovation Center of Medicine & Engineering of Guangdong Medical University No. 4SG22317PTalent Development Foundation of The First Dongguan Affiliated Hospital of Guangdong Medical University No. PU2023003
6 · The paper itself

Abstract

backgroundImmune evasion by Mycobacterium tuberculosis (Mtb) complicates tuberculosis (TB) therapy. Ferroptosis, an iron-dependent form of regulated cell death, is increasingly recognized as a critical process in host-pathogen interactions. We aimed to define the role of poly(C)-binding protein 1 (PCBP1) in macrophage ferroptosis during Mtb infection and to develop a targeted RNA activation (RNAa) nanotherapy to exploit this pathway.

methodsWe analyzed clinical samples from TB patients and investigated Mtb-host interactions in macrophage models using molecular and biochemical assays. Mannosylated lipid nanoparticles (MLNPs) were engineered to deliver PCBP1-targeting small activating RNAs (saRNAs). Therapeutic efficacy, lung-specific delivery, and biocompatibility were evaluated in a murine TB model.

resultsMtb utilizes the host E3 ubiquitin ligase Trim21 to mediate the proteasomal degradation of PCBP1. PCBP1 loss induced macrophage ferroptosis by modulating its downstream targets GPX4, PTGS2, and HMOX1, promoting bacterial survival. In vitro, saPCBP1@MLNPs restored PCBP1 expression, reversed ferroptosis markers (Fe²⁺, 4-HNE), and reduced Mtb burden. In murine models, the nanotherapy achieved lung-specific delivery, significantly attenuated lung pathology, and enhanced bacterial clearance.

conclusionsPCBP1 is a critical, druggable immune-metabolic checkpoint that governs macrophage ferroptosis in TB. Our targeted RNAa nanotherapy represents a promising host-directed strategy for Mtb infection, linking a key molecular mechanism to a translational therapeutic platform and offering a new approach for treating drug-resistant TB.

Indexed as

DNA-Binding ProteinsFerroptosisMacrophagesMycobacterium tuberculosisRNA-Binding ProteinsTuberculosisAnimalsFemaleHost-Directed TherapyHost-Pathogen InteractionsHumansLungMiceMice, Inbred C57BLNanoparticlesDNA-Binding ProteinsPCBP1 protein, humanRNA-Binding ProteinsFerroptosisHost-directed therapyMycobacterium tuberculosisNanotherapyPCBP1RNA activation (RNAa)

Identifiers

PMID42168992
PMCPMC13377778

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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.