Evidence map›Paper›PMID 35858897›Full record

ArticleStem cell research & therapy2022

Mesenchymal stem cell-derived exosomes protect against liver fibrosis via delivering miR-148a to target KLF6/STAT3 pathway in macrophages.

Siyuan Tian, Xia Zhou, Miao Zhang, Lina Cui, Bo Li, Yansheng Liu, Rui Su, Keshuai Sun, Yinan Hu, Fangfang Yang and 8 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 2 pooled it
10.5field-weighted citation impact, top 1% 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

95 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.

  1. Pooled it
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  6. [Mesenchymal stem cell-derived exosomes: a new hope for metabolic-associated fatty liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
    Review
  7. Liver Macrophages in the Pathogenesis of Viral Hepatitis.Current issues in molecular biology · 2026
    Review
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35 more citing papers are in PubMed but not listed here.

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

18 authors at 1 institution in 1 country.

Siyuan Tian *State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Xia Zhou *State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Miao Zhang *State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Lina Cui *State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Bo LiState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Yansheng LiuState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Rui SuState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Keshuai SunDepartment of Gastroenterology, The Air Force Hospital From Eastern Theater of PLA, Nanjing, 210002, Jiangsu, China.
Yinan HuState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Fangfang YangState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Guoyun XuanState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Shuoyi MaState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Xiaohong ZhengState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Xinmin ZhouState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Changcun GuoState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Yulong ShangState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. shangyul870222@163.com.
Jingbo WangState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. jbwang002@163.com.
Ying HanState Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. hanying1@fmmu.edu.cn.ORCID 0000-0003-3046-9507
Xijing Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDespite emerging evidence on the therapeutic potential of mesenchymal stem cells (MSCs) for liver fibrosis, the underlying mechanisms remain unclear. At present, MSC-derived exosomes (MSC-EXOs) are widely accepted as crucial messengers for intercellular communication. This study aimed to explore the therapeutic effects of MSC-EXOs on liver fibrosis and identify the mechanisms underlying the action of MSC-EXOs.

methodsCarbon tetrachloride was used to induce a liver fibrosis model, which was intravenously administered with MSCs or MSC-EXOs to assess treatment efficacy. The resulting histopathology, fibrosis degree, inflammation and macrophage polarization were analyzed. RAW264.7 and BMDM cells were used to explore the regulatory effects of MSC-EXOs on macrophage polarization. Then, the critical miRNA mediating the therapeutic effects of MSC-EXOs was screened via RNA sequencing and validated experimentally. Furthermore, the target mRNA and downstream signaling pathways were elucidated by luciferase reporter assay, bioinformatics analysis and western blot.

resultsMSCs alleviated liver fibrosis largely depended on their secreted exosomes, which were visualized to circulate into liver after transplantation. In addition, MSC-EXOs were found to modulate macrophage phenotype to regulate inflammatory microenvironment in liver and repair the injury. Mechanically, RNA-sequencing illustrates that miR-148a, enriched in the MSC-EXOs, targets Kruppel-like factor 6 (KLF6) to suppress pro-inflammatory macrophages and promote anti-inflammatory macrophages by inhibiting the STAT3 pathway. Administration of miR-148a-enriched MSC-EXOs or miR-148a agomir shows potent ameliorative effects on liver fibrosis.

conclusionsThese findings suggest that MSC-EXOs protect against liver fibrosis via delivering miR-148a that regulates intrahepatic macrophage functions through KLF6/STAT3 signaling and provide a potential therapeutic target for liver fibrosis.

Indexed as

ExosomesMesenchymal Stem CellsMicroRNAsHumansKruppel-Like Factor 6Liver CirrhosisMacrophagesSTAT3 Transcription FactorKLF6 protein, humanKruppel-Like Factor 6MicroRNAsSTAT3 protein, humanSTAT3 Transcription FactorExosomeLiver fibrosisMacrophage polarizationMesenchymal stem cellsmiR-148a

Identifiers

PMID35858897
PMCPMC9297598
OpenAlexW4285891338

What OpenQuestion holds

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LicenceCC BY
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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.