Evidence map›Paper›PMID 39252766›Full record

ArticleDrug design, development and therapy2024

Trimetazidine Alleviates Bleomycin-Induced Pulmonary Fibrosis by Targeting the Long Noncoding RNA CBR3-AS1-Mediated miRNA-29 and Resistin-Like Molecule alpha 1: Deciphering a Novel Trifecta Role of LncRNA CBR3-AS1/miRNA-29/FIZZ1 Axis in Lung Fibrosis.

Abdullah R Alzahrani, Doaa I Mohamed, Hebatallah H Abo Nahas, Dalia Alaa El-Din Aly El-Waseef, Abdulmalik S Altamimi, Ibrahim H Youssef, Ibrahim Abdel Aziz Ibrahim, Soha M Y Mohamed, Yasmine Gamal Sabry, Alaa H Falemban and 4 more

Abstract read
In one paragraph

Article in Drug design, development and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Review
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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

14 authors.

Abdullah R AlzahraniDepartment of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Doaa I MohamedDepartment of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Hebatallah H Abo NahasZoology Department, Faculty of Science, Port Said University, Port Said, Egypt.
Dalia Alaa El-Din Aly El-WaseefDepartment of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.ORCID 0000-0001-8199-2512
Abdulmalik S AltamimiDepartment of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia.
Ibrahim H YoussefDepartment of Chest Diseases, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
Ibrahim Abdel Aziz IbrahimDepartment of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Soha M Y MohamedPhysiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.ORCID 0009-0006-1404-0187
Yasmine Gamal SabryPhysiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Alaa H FalembanDepartment of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.ORCID 0000-0002-1335-1788
Nasser Attia ElhawaryDepartment of Medical Genetics, College of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia.ORCID 0000-0002-9137-351X
Ghazi A BamagousDepartment of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Mariusz JaremkoSmart-Health Initiative and Red Sea Research Center, Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
Essa M SaiedChemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt.ORCID 0000-0002-7342-6200

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Pulmonary fibrosis (PF) and tissue remodeling can greatly impair pulmonary function and often lead to fatal outcomes. Methodology: In the present study, we explored a novel molecular interplay of long noncoding (Lnc) RNA CBR3-AS1/ miRNA-29/ FIZZ1 axis in moderating the inflammatory processes, immunological responses, and oxidative stress pathways in bleomycin (BLM)-induced lung fibrosis. Furthermore, we investigated the pharmacological potential of Trimetazidine (TMZ) in ameliorating lung fibrosis. Results: Our results revealed that the BLM-treated group exhibited a significant upregulation in the expression of epigenetic regulators, lncRNA CBR3-AS1 and FIZZ1, compared to the control group (P<0.0001), along with the downregulation of miRNA-29 expression. Furthermore, Correlation analysis showed a significant positive association between lnc CBR3-AS1 and FIZZ1 (R=0.7723, p<0.05) and a significant negative association between miRNA-29 and FIZZ1 (R=-0.7535, p<0.05), suggesting lnc CBR3-AS1 as an epigenetic regulator of FIZZ1 in lung fibrosis. BLM treatment significantly increased the expression of Notch, Jagged1, Smad3, TGFB1, and hydroxyproline. Interestingly, the administration of TMZ demonstrated the ability to attenuate the deterioration effects caused by BLM treatment, as indicated by biochemical and histological analyses. Our investigations revealed that the therapeutic potential of TMZ as an antifibrotic drug could be ascribed to its ability to directly target the epigenetic regulators lncRNA CBR3-AS1/ miRNA-29/ FIZZ1, which in turn resulted in the mitigation of lung fibrosis. Histological and immunohistochemical analyses further validated the potential antifibrotic effects of TMZ by mitigating the structural damage associated with fibrosis. Discussion: Taken together, our study showed for the first time the interplay between epigenetic lncRNAs CBR3-AS1 and miRNA-29 in lung fibrosis and demonstrated that FIZZ1 could be a downregulatory gene for lncRNA CBR3-AS1 and miRNA-29. Our key findings demonstrate that TMZ significantly reduces the expression of fibrotic, oxidative stress, immunomodulatory, and inflammatory markers, along with epigenetic regulators associated with lung fibrosis. This validates its potential as an effective antifibrotic agent by targeting the CBR3-AS1/miRNA-29/FIZZ1 axis.

Indexed as

BleomycinMicroRNAsPulmonary FibrosisRNA, Long NoncodingTrimetazidineAnimalsMaleMiceMice, Inbred C57BLBleomycinMicroRNAsMIRN29 microRNA, mouseRNA, Long NoncodingTrimetazidineFIZZ1histopathologylong noncoding RNA CBR3-AS1lung fibrosismiRNA-29trimetazidine

Identifiers

PMID39252766
PMCPMC11382803

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LicenceCC BY-NC
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Registered trials

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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.