Evidence map›Paper›PMID 31249375›Full record

ArticleLaboratory investigation; a journal of technical methods and pathology2019

Thy-1 depletion and integrin β3 upregulation-mediated PI3K-Akt-mTOR pathway activation inhibits lung fibroblast autophagy in lipopolysaccharide-induced pulmonary fibrosis.

Hanxi Wan, Tingting Xie, Qiaoyi Xu, Xiaoting Hu, Shunpeng Xing, Hao Yang, Yuan Gao, Zhengyu He

Open access · bronzeAbstract read
In one paragraph

Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.9field-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

39 citing papers in PubMed, 61 citations in OpenAlex.

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  14. LAMA4Cell communication and signaling : CCS · 2025
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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

8 authors at 2 institutions in 1 country.

Hanxi WanDepartment of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 200127, Shanghai, China.
Tingting XieDepartment of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 200127, Shanghai, China.
Qiaoyi XuDepartment of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 200127, Shanghai, China.
Xiaoting HuDepartment of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 200127, Shanghai, China.
Shunpeng XingDepartment of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 200127, Shanghai, China.
Hao YangDepartment of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433, Shanghai, China.
Yuan GaoDepartment of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 200127, Shanghai, China. rj_gaoyuan@163.com.
Zhengyu HeDepartment of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 200127, Shanghai, China. zhengyuheshsmu@163.com.
Renji Hospital · CNTongji University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipopolysaccharide (LPS)-induced autophagy inhibition in lung fibroblasts is closely associated with the activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K-Akt-mTOR) pathway. However, the underlying mechanism remains unknown. In this study, we demonstrated that LPS activated the PI3K-Akt-mTOR pathway and inhibited lung fibroblast autophagy by depleting thymocyte differentiation antigen-1 (Thy-1) and upregulating integrin β3 (Itgb3). Challenge of the human lung fibroblast MRC-5 cell line with LPS resulted in significant upregulation of integrin β3, activation of the PI3K-Akt-mTOR pathway and inhibition of autophagy, which could be abolished by integrin β3 silencing by specific shRNA or treatment with the integrin β3 inhibitor cilengitide. Meanwhile, LPS could inhibit Thy-1 expression accompanied with PI3K-Akt-mTOR pathway activation and lung fibroblast autophagy inhibition; these effects could be prevented by Thy-1 overexpression. Meanwhile, Thy-1 downregulation with Thy-1 shRNA could mimic the effects of LPS, inducing the activation of PI3K-Akt-mTOR pathway and inhibiting lung fibroblast autophagy. Furthermore, protein immunoprecipitation analysis demonstrated that LPS reduced the binding of Thy-1 to integrin β3. Thy-1 downregulation, integrin β3 upregulation and autophagy inhibition were also detected in a mouse model of LPS-induced pulmonary fibrosis, which could be prohibited by intratracheal injection of Thy-1 overexpressing adeno-associated virus (AAV) or intraperitoneal injection of the integrin β3 inhibitor cilengitide. In conclusion, this study demonstrated that Thy-1 depletion and integrin β3 upregulation are involved in LPS-induced pulmonary fibrosis, and may serve as potential therapeutic targets for pulmonary fibrosis.

Indexed as

AnimalsAutophagyCell LineDisease Models, AnimalFibroblastsHumansIntegrin beta3LipopolysaccharidesLungMaleMiceMice, Inbred C57BLMicroscopy, Electron, TransmissionPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPulmonary FibrosisIntegrin beta3LipopolysaccharidesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktThy-1 AntigensTOR Serine-Threonine Kinases

Identifiers

PMID31249375
PMCPMC7102294
OpenAlexW2953593976

What OpenQuestion holds

Textmetadata
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.