Evidence map›Paper›PMID 26956419›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016

Contribution of the anaphylatoxin receptors, C3aR and C5aR, to the pathogenesis of pulmonary fibrosis.

Hongmei Gu, Amanda J Fisher, Elizabeth A Mickler, Frank Duerson, Oscar W Cummings, Marc Peters-Golden, Homer L Twigg, Trent M Woodruff, David S Wilkes, Ragini Vittal

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.9field-weighted citation impact, top 5% 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

59 citing papers in PubMed, 95 citations in OpenAlex.

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  9. Emerging roles for complement in lung transplantation.The Journal of clinical investigation · 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

10 authors at 4 institutions in 2 countries.

Hongmei GuDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA;
Amanda J FisherDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA;
Elizabeth A MicklerDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA;
Frank DuersonDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA;
Oscar W CummingsDepartment of Pathology, Indiana University School of Medicine, Indianapolis, Indiana, USA;
Marc Peters-GoldenDivision of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Homer L TwiggDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA;
Trent M WoodruffSchool of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.
David S WilkesDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA;
Ragini VittalDivision of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA rvittal@med.umich.edu.
Indiana University – Purdue University Indianapolis · USIndiana University School of MedicineUniversity of Michigan–Ann Arbor · USUniversity of Queensland · AU

Funding

Control of Fibroblast Function by Prostaglandin E2 and Plasminogen ActivationR01HL094311 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PETERS-GOLDEN, MARC L · 2009 to 2017
$3.4M
Role of IL-17 in the Induction of Epithelial to Mesenchymal TransitionR01HL109288 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI VITTAL, RAGINI · 2011 to 2015
$1.9M
NHLBI NIH HHS R01 HL094311NHLBI NIH HHS R01 HL109288
6 · The paper itself

Abstract

Complement activation, an integral arm of innate immunity, may be the critical link to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Whereas we have previously reported elevated anaphylatoxins-complement component 3a (C3a) and complement component 5a (C5a)-in IPF, which interact with TGF-β and augment epithelial injury in vitro, their role in IPF pathogenesis remains unclear. The objective of the current study is to determine the mechanistic role of the binding of C3a/C5a to their respective receptors (C3aR and C5aR) in the progression of lung fibrosis. In normal primary human fetal lung fibroblasts, C3a and C5a induces mesenchymal activation, matrix synthesis, and the expression of their respective receptors. We investigated the role of C3aR and C5aR in lung fibrosis by using bleomycin-injured mice with fibrotic lungs, elevated local C3a and C5a, and overexpression of their receptors via pharmacologic and RNA interference interventions. Histopathologic examination revealed an arrest in disease progression and attenuated lung collagen deposition (Masson's trichrome, hydroxyproline, collagen type I α 1 chain, and collagen type I α 2 chain). Pharmacologic or RNA interference-specific interventions suppressed complement activation (C3a and C5a) and soluble terminal complement complex formation (C5b-9) locally and active TGF-β1 systemically. C3aR/C5aR antagonists suppressed local mRNA expressions of tgfb2, tgfbr1/2, ltbp1/2, serpine1, tsp1, bmp1/4, pdgfbb, igf1, but restored the proteoglycan, dcn Clinically, compared with pathologically normal human subjects, patients with IPF presented local induction of C5aR, local and systemic induction of soluble C5b-9, and amplified expression of C3aR/C5aR in lesions. The blockade of C3aR and C5aR arrested the progression of fibrosis by attenuating local complement activation and TGF-β/bone morphologic protein signaling as well as restoring decorin, which suggests a promising therapeutic strategy for patients with IPF.-Gu, H., Fisher, A. J., Mickler, E. A., Duerson, F., III, Cummings, O. W., Peters-Golden, M., Twigg, H. L., III, Woodruff, T. M., Wilkes, D. S., Vittal, R. Contribution of the anaphylatoxin receptors, C3aR and C5aR, to the pathogenesis of pulmonary fibrosis.

Indexed as

AgedAged, 80 and overAnimalsAntibiotics, AntineoplasticBleomycinCell LineCollagen Type I, alpha 1 ChainComplement Membrane Attack ComplexDown-RegulationFibroblastsGene Expression RegulationHumansLung InjuryMiceMice, Inbred C57BLMiddle AgedAntibiotics, AntineoplasticBleomycinCOL1A1 protein, humanCollagen Type I, alpha 1 Chaincomplement C3a receptorComplement Membrane Attack ComplexReceptor, Anaphylatoxin C5aReceptors, ComplementTransforming Growth Factor betaBMPC5b-9decorinIPFTGF-β1

Identifiers

PMID26956419
PMCPMC4871799
OpenAlexW2293956792

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.