Evidence map›Paper›PMID 40634394›Full record

ArticleScientific reports2025

Knockdown of RGMa reduces vascular calcification by inhibiting the AKT signaling pathway.

Hongmei Xiao, Guanru Shen, Zijie Wang, Xiaofan Yuan, Yue Ma, Ruiqi Cheng, Xinyue Qin

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. Not yet cited in PubMed.

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

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

7 authors.

Hongmei Xiao *Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Guanru Shen *Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Zijie WangDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xiaofan YuanDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Yue MaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Ruiqi ChengDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xinyue QinDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. qinxy20021@sina.com.

Funding

National Natural Science Foundation of China 82071338Natural Science Foundation of Sichuan Province 24NSFSC2240
6 · The paper itself

Abstract

Vascular calcification (VC), pathologically characterized by ectopic calcium-phosphate deposition, demonstrates a significant correlation with cardio-cerebrovascular morbidity and adverse clinical outcomes. Despite its clinical relevance, current interventions to prevent and treat VC progression remain limited in efficacy. Numerous studies have demonstrated that Repulsive Guidance Molecule A (RGMa) plays a pivotal role in cardio-cerebrovascular diseases. This investigation aimed to elucidate the role of RGMa in VC and to explore the underlying molecular mechanisms. This study systematically investigated the dynamic alterations in RGMa expression during VC progression through integrated in vitro and in vivo experimental models. The functional regulatory role of RGMa in VC pathogenesis and its molecular mechanistic basis were further elucidated via lentiviral short hairpin RNA (shRNA)-mediated RGMa knockdown and adeno-associated virus serotype 9 (AAV9)-delivered gene silencing, combined with pharmacological inhibition of AKT signaling using the selective inhibitor MK-2206. Alizarin Red S staining and calcium content assays demonstrated that VC and vascular smooth muscle cell (VSMC) calcification were successfully induced in vivo (via subcutaneous vitamin D3 overdose) and in vitro (through high-phosphate medium culture), respectively. Western blot (WB) and immunofluorescence (IF) analyses revealed a significant upregulation of RGMa expression in calcified VSMCs. We successfully constructed a VSMC-specific RGMa-targeting AAV, and RGMa knockdown effectively attenuated VC. These findings indicate that RGMa plays a pivotal role in VSMC calcification. Finally, we investigated whether RGMa exerts its effects via the AKT pathway. In the in vitro model, treatment with the AKT inhibitor MK-2206 suppressed osteogenic marker expression in high phosphate-treated VSMCs without reversing RGMa upregulation. This study indicates that RGMa may promote VC by modulating AKT activation, highlighting RGMa as a promising new molecular target for the treatment of VC.

Indexed as

GPI-Linked ProteinsNerve Tissue ProteinsProto-Oncogene Proteins c-aktSignal TransductionVascular CalcificationAnimalsDisease Models, AnimalGene Knockdown TechniquesHeterocyclic Compounds, 3-RingHumansMaleMiceMuscle, Smooth, VascularMyocytes, Smooth MuscleGPI-Linked ProteinsHeterocyclic Compounds, 3-RingMK 2206Nerve Tissue ProteinsProto-Oncogene Proteins c-aktAKT signaling pathwayRGMaVascular calcificationVitD3VSMCs

Identifiers

PMID40634394
PMCPMC12241471

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.