Evidence map›Paper›PMID 37948857›Full record

ArticleInternational immunopharmacology2023

C5a/C5aR1 axis as a key driver promotes epithelial-to-mesenchymal transition in airway epithelial cells in silica nanoparticles-induced pulmonary fibrosis.

Sifan Zhou, Zhoujian Wang, Lei Gao, Muyue Chen, Yuansheng Duan, Pengcheng Zhou, Zhibing Liu, Changhao Wu, Jiaxiang Zhang, Qixing Zhu

Open access · greenAbstract read
In one paragraph

Article in International immunopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

2 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
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

10 authors at 2 institutions in 2 countries.

Sifan ZhouDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Zhoujian WangDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Lei GaoDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Muyue ChenDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Yuansheng DuanDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Pengcheng ZhouDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Zhibing LiuDepartment of Dermatology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, China.
Changhao WuDepartment of Biochemistry and Physiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
Jiaxiang ZhangDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China. Electronic address: jiaxiang5337@ahmu.edu.cn.
Qixing ZhuDepartment of Dermatology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, China. Electronic address: zqxing@yeah.net.
Anhui Medical University · CNUniversity of Surrey · GB

Funding

Nox Enzymes in Aging Bladder DysfunctionR01AG049321 · NIA · TEMPLE UNIV OF THE COMMONWEALTH · PI BARBE, MARY F · 2016 to 2020
$1.7M
NIA NIH HHS R01 AG049321
6 · The paper itself

Abstract

Previous studies have shown that silica nanoparticles (SiNPs) exposure can affect the respiratory, cardiovascular, reproductive and other systems, with the lung being the primary target organ for the direct effect, causing damage with a central feature of pulmonary inflammation and fibrosis. However, the underlying mechanisms of pulmonary fibrosis due to SiNPs are not fully understood. The aim of the study was to investigate the role of complement anaphylatoxin C5a in SiNPs-induced pulmonary fibrosis. A mouse model of SiNPs-induced pulmonary fibrosis was established, and pulmonary fibrosis-related indicators, epithelial-to-mesenchymal transition (EMT), C5a/C5aR1 and high mobility group protein B1 (HMGB1) proteins were measured. An in vitro study using the human lung epithelial cell line BEAS-2B investigated whether C5a leads to epithelial-to-mesenchymal trans-differentiation. In vivo studies revealed that SiNPs-induced pulmonary fibrosis mainly manifested as EMT trans-differentiation in airway epithelial cells, which subsequently led to excessive deposition of extracellular matrix (ECM). Furthermore, we found that C5a and C5aR1 proteins were also increased in SiNPs-induced pulmonary fibrosis tissue. In vitro studies also showed that C5a directly activated HMGB1/RAGE signaling and induced EMT in BEAS-2B cells. Finally, treatment of SiNPs-exposed mice with the C5aR1 inhibitor PMX205 effectively reduced C5aR1 levels and inhibited the activation of HMGB1/RAGE signaling and the expression of EMT-related proteins, culminating in a significant alleviation of pulmonary fibrosis. Taken together, our results suggest that C5a/C5aR1 is the main signaling pathway for SiNPs-induced pulmonary fibrosis, which induces EMT in airway epithelial cells via the HMGB1/RAGE axis.

Indexed as

HMGB1 ProteinNanoparticlesPulmonary FibrosisAnimalsComplement C5aEpithelial CellsHumansMiceReceptor, Anaphylatoxin C5aSilicon DioxideComplement C5aHMGB1 ProteinReceptor, Anaphylatoxin C5aSilicon DioxideC5a/C5aR1 axisEMTHMGB1Pulmonary fibrosisSilica nanoparticles

Identifiers

PMID37948857
PMCPMC12076580
OpenAlexW4388483789

What Socratic holds

Textmetadata
LicenceTDM
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.