Evidence map›Paper›PMID 40045202›Full record

ArticleMolecular medicine (Cambridge, Mass.)2025

miR-6516-3p-mediated downregulation of the endogenous MMP-9 inhibitor RECK in mesangial cells might exacerbate lupus nephritis.

Hiroyuki Tomita, Kunihiro Hayakawa, Keigo Ikeda, Hiroshi Tsushima, Marina Shinoura, Maki Fujishiro, Yuko Kataoka, Ken Yamaji, Kenji Takamori, Naoto Tamura and 2 more

Abstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 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

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

1 citing paper in PubMed.

  1. Matrix Metalloproteinases in Inflammatory Dermatoses.International journal of molecular sciences · 2025
    Review
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

12 authors.

Hiroyuki TomitaInstitute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu-Shi, Chiba, 279-0021, Japan.
Kunihiro HayakawaInstitute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu-Shi, Chiba, 279-0021, Japan.
Keigo IkedaInstitute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu-Shi, Chiba, 279-0021, Japan. keigo@juntendo.ac.jp.ORCID 0000-0002-8032-7147
Hiroshi TsushimaDepartment of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Marina ShinouraInstitute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu-Shi, Chiba, 279-0021, Japan.
Maki FujishiroInstitute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu-Shi, Chiba, 279-0021, Japan.
Yuko KataokaInstitute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu-Shi, Chiba, 279-0021, Japan.
Ken YamajiDepartment of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Kenji TakamoriInstitute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu-Shi, Chiba, 279-0021, Japan.
Naoto TamuraDepartment of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Iwao SekigawaInstitute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu-Shi, Chiba, 279-0021, Japan.
Shinji MorimotoInstitute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu-Shi, Chiba, 279-0021, Japan.

Funding

Japan Society for the Promotion of Science (JSPS) KAKENHI JP19K09608Japan Society for the Promotion of Science (JSPS) KAKENHI JP22K09365Ministry of Education, Culture, Sports, Science, and Technology (MEXT) S1311011
6 · The paper itself

Abstract

backgroundMicroRNAs (miRNAs) regulate biological processes by inhibiting translation and causing mRNA degradation. In this study, we identified the miRNAs involved in the development and progression of lupus nephritis (LNs) and verified their roles.

methodsTotal RNA, extracted from PBMCs collected from patients with LNs before and after treatment, was used for miRNA array analysis to identify miRNAs whose expression was significantly altered. The results of this analysis were confirmed using qRT-PCR. The identified miRNAs were transfected into normal human mesangial cells (NHMCs), human renal proximal tubule epithelial cells (RPTECs), human umbilical vein endothelial cells (HUVECs), and THP-1-derived macrophages (THP1-Mφ) to investigate their biological functions.

resultsThree miRNAs were altered in PBMCs before and after treatment of LNs. Among these miRNAs, hsa-miR-6516-3p promoted TNF-α-induced expression of MMP-9 in NHMCs. Moreover, hsa-miR-6516-3p downregulated the expression of RECK, an endogenous inhibitor of MMP-9. However, in NHMCs, endogenous hsa-miR-6516-3p was not present in functional amounts under inflammatory environment; therefore, we performed analysis using an experimental system considering extracellular influences of mesangial cells under LNs. The expression of hsa-miR-6516-3p was increased in HUVECs under inflammatory conditions and in activated macrophages.

conclusionshsa-miR-6516-3p increases MMP9 expression by suppressing RECK, and might, thereby, exacerbate LNs.

Indexed as

GPI-Linked ProteinsLupus NephritisMatrix Metalloproteinase 9Mesangial CellsMicroRNAsDown-RegulationFemaleGene Expression RegulationHumansHuman Umbilical Vein Endothelial CellsMacrophagesTumor Necrosis Factor-alphaGPI-Linked ProteinsMatrix Metalloproteinase 9MicroRNAsRECK protein, humanTumor Necrosis Factor-alphaLupus nephritismicroRNA (miRNA)miR-6516-3pMMP-9Normal human glomerular mesangial cells (NHMC)RECKSystemic lupus erythematosus (SLE)

Identifiers

PMID40045202
PMCPMC11881388

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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.