Evidence map›Paper›PMID 35624154›Full record

ArticleExperimental & molecular medicine2022

TGF-β promotes pericyte-myofibroblast transition in subretinal fibrosis through the Smad2/3 and Akt/mTOR pathways.

Zhenzhen Zhao, Yumeng Zhang, Chaoyang Zhang, Jingting Zhang, Xueting Luo, Qinghua Qiu, Dawei Luo, Jingfa Zhang

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Experimental & molecular medicine, 2022. 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 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
18.0field-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

68 citing papers in PubMed, 96 citations in OpenAlex.

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8 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 3 countries.

Zhenzhen Zhao *Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Yumeng Zhang *Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Chaoyang ZhangDepartment of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Jingting ZhangDepartment of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Xueting LuoDepartment of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Qinghua QiuDepartment of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Dawei LuoDepartment of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Jingfa ZhangDepartment of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai, China. jingfa.zhang@shgh.cn.ORCID http://orcid.org/0000-0003-0601-4342
Shanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Subretinal fibrosis remains a major obstacle to the management of neovascular age-related macular degeneration. Choroidal pericytes were found to be a significant source of subretinal fibrosis, but the underlying mechanisms of pericyte-myofibroblast transition (PMT) remain largely unknown. The goal of this study was to explore the role and potential mechanisms by which PMT contributes to subretinal fibrosis. Choroidal neovascularization (CNV) was induced by laser photocoagulation in transgenic mice with the collagen1α1-green fluorescent protein (Col1α1-GFP) reporter, and recombinant adeno-associated virus 2 (rAAV2)-mediated TGF-β2 (rAAV2-TGF-β2) was administered intravitreally to further induce PMT. Primary mouse choroidal GFP-positive pericytes were treated with TGF-β2 in combination with siRNAs targeting Smad2/3, the Akt inhibitor MK2206 or the mTOR inhibitor rapamycin to examine cell proliferation, migration, and differentiation into myofibroblasts. The involvement of the Akt/mTOR pathway in PMT in subretinal fibrosis was further investigated in vivo. Intraocular TGF-β2 overexpression induced GFP-positive pericyte infiltration and PMT in subretinal fibrosis, which was mimicked in vitro. Knockdown of Smad2/3 or inhibition of Akt/mTOR decreased cell proliferation, PMT and migration in primary mouse pericytes. Combined inhibition of Smad2/3 and mTOR showed synergistic effects on attenuating α-smooth muscle actin (α-SMA) expression and cell proliferation. In mice with laser-induced CNV, the administration of the Akt/mTOR inhibitors suppressed pericyte proliferation and alleviated the severity of subretinal fibrosis. Our results showed that PMT plays a pivotal role in subretinal fibrosis, which was induced by TGF-β2 through the Smad2/3 and Akt/mTOR pathways. Thus, inhibiting PMT may be a novel strategy for the treatment of subretinal fibrosis.

Indexed as

MyofibroblastsPericytesAnimalsFibrosisMiceProto-Oncogene Proteins c-aktSmad2 ProteinSmad3 ProteinTOR Serine-Threonine KinasesTransforming Growth Factor beta2Proto-Oncogene Proteins c-aktSmad2 ProteinSmad2 protein, mouseSmad3 ProteinSmad3 protein, mouseTOR Serine-Threonine KinasesTransforming Growth Factor beta2

Identifiers

PMID35624154
PMCPMC9166792
OpenAlexW4281807769

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.