Evidence map›Paper›PMID 32787856›Full record

ArticleCell communication and signaling : CCS2020

Metabolic syndrome increases senescence-associated micro-RNAs in extracellular vesicles derived from swine and human mesenchymal stem/stromal cells.

Yongxin Li, Yu Meng, Xiangyang Zhu, Ishran M Saadiq, Kyra L Jordan, Alfonso Eirin, Lilach O Lerman

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
4.5field-weighted citation impact, top 4% of its field
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

22 citing papers in PubMed, 57 citations in OpenAlex.

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  14. Role of microRNAs in Obesity-Related Kidney Disease.International journal of molecular sciences · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Yongxin LiDivision of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Yu MengDepartment of Nephrology, The First Hospital Affiliated to Jinan University, Guangzhou, 510630, People's Republic of China.
Xiangyang ZhuDivision of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Ishran M SaadiqDivision of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Kyra L JordanDivision of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Alfonso EirinDivision of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Lilach O LermanDivision of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Lerman.Lilach@Mayo.edu.ORCID 0000-0002-3271-3887
Mayo Clinic · USFirst Affiliated Hospital of Jinan University · CNQingdao University · CN

Funding

MSC-derived microvesicles in metabolic syndrome and renovascular diseaseR01DK102325 · NIDDK · MAYO CLINIC ROCHESTER · PI LERMAN, LILACH O · 2015 to 2018
$2.8M
Obesity-induced mesenchymal stem cell senescenceR01DK120292 · NIDDK · MAYO CLINIC ROCHESTER · PI LERMAN, LILACH O · 2019 to 2022
$2.6M
Quantitative magnetization transfer MRI for evaluation of renal fibrosisR01DK122734 · NIDDK · MAYO CLINIC ROCHESTER · PI LERMAN, LILACH O · 2020 to 2023
$2.2M
A potential role for mitoprotection in preserving the kidney in metabolic syndrome and renal artery stenosisK08DK106427 · NIDDK · MAYO CLINIC ROCHESTER · PI EIRIN, ALFONSO · 2015 to 2019
$819k
Mitochondrial injury interferes with endogenous renal repair in experimental renovascular diseaseR03DK122137 · NIDDK · MAYO CLINIC ROCHESTER · PI EIRIN, ALFONSO · 2019 to 2020
$239k
NIDDK NIH HHS K08 DK106427NIDDK NIH HHS R01 DK102325NIDDK NIH HHS R01 DK120292NIDDK NIH HHS R01 DK122734NIDDK NIH HHS R03 DK122137
6 · The paper itself

Abstract

backgroundThe metabolic syndrome (MetS) is a combination of cardiovascular risk-factors, including obesity, hypertension, hyperglycemia, and insulin resistance. MetS may induce senescence in mesenchymal stem/stromal cells (MSC) and impact their micro-RNA (miRNA) content. We hypothesized that MetS also alters senescence-associated (SA) miRNAs in MSC-derived extracellular vesicles (EVs), and interferes with their function.

methodsEVs were collected from abdominal adipose tissue-derived MSCs from pigs with diet-induced MetS or Lean controls (n = 6 each), and from patients with MetS (n = 4) or age-matched Lean controls (n = 5). MiRNA sequencing was performed to identify dysregulated miRNAs in these EVs, and gene ontology to analyze their SA-genes targeted by dysregulated miRNAs. To test for EV function, MetS and Lean pig-EVs were co-incubated with renal tubular cells in-vitro or injected into pigs with renovascular disease (RVD, n = 6 each) in-vivo. SA-b-Galactosidase and trichrome staining evaluated cellular senescence and fibrosis, respectively.

resultsBoth humans and pigs with MetS showed obesity, hypertension, and hyperglycemia/insulin resistance. In MetS pigs, several upregulated and downregulated miRNAs targeted 5768 genes in MSC-EVs, 68 of which were SA. In MetS patients, downregulated and upregulated miRNAs targeted 131 SA-genes, 57 of which overlapped with pig-EVs miRNA targets. In-vitro, MetS-MSC-EVs induced greater senescence in renal tubular cells than Lean-MSC-EVs. In-vivo, Lean-MSC-EVs attenuated renal senescence, fibrosis, and dysfunction more effectively than MetS-MSC-EVs.

conclusionsMetS upregulates SA-miRNAs in swine MSC-EVs, which is conserved in human subjects, and attenuates their ability to blunt cellular senescence and repair injured target organs. These alterations need to be considered when designing therapeutic regenerative approaches. Video abstract.

Indexed as

Cellular SenescenceAdultAnimalsCell LineDisease Models, AnimalExtracellular VesiclesFemaleGene Expression RegulationHumansKidneyMesenchymal Stem CellsMetabolic SyndromeMicroRNAsSwineThinnessYoung AdultMicroRNAsEVMetabolic syndromeMSCRNA-sequencingSenescence

Identifiers

PMID32787856
PMCPMC7425605
OpenAlexW3048895709

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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.