Evidence map›Paper›PMID 35015734›Full record

ArticleJCI insight2022

A single-domain i-body, AD-114, attenuates renal fibrosis through blockade of CXCR4.

Qinghua Cao, Chunling Huang, Hao Yi, Anthony J Gill, Angela Chou, Michael Foley, Chris G Hosking, Kevin K Lim, Cristina F Triffon, Ying Shi and 2 more

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

Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.8field-weighted citation impact, top 13% 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

12 citing papers in PubMed, 17 citations in OpenAlex.

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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

12 authors at 3 institutions in 1 country.

Qinghua CaoRenal Medicine, Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Chunling HuangRenal Medicine, Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Hao YiRenal Medicine, Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Anthony J GillDepartment of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
Angela ChouDepartment of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
Michael FoleyThe Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Chris G HoskingThe Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Kevin K LimThe Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Cristina F TriffonThe Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Ying ShiRenal Medicine, Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Xin-Ming ChenRenal Medicine, Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Carol A PollockRenal Medicine, Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Advanced Medical Institute (Australia) · AULa Trobe University · AURoyal North Shore Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The G protein-coupled CXC chemokine receptor 4 (CXCR4) is a candidate therapeutic target for tissue fibrosis. A fully human single-domain antibody-like scaffold i-body AD-114-PA600 (AD-114) with specific high binding affinity to CXCR4 has been developed. To define its renoprotective role, AD-114 was administrated in a mouse model of renal fibrosis induced by folic acid (FA). Increased extracellular matrix (ECM) accumulation, macrophage infiltration, inflammatory response, TGF-β1 expression, and fibroblast activation were observed in kidneys of mice with FA-induced nephropathy. These markers were normalized or partially reversed by AD-114 treatment. In vitro studies demonstrated AD-114 blocked TGF-β1-induced upregulated expression of ECM, matrix metalloproteinase-2, and downstream p38 mitogen-activated protein kinase (p38 MAPK) and PI3K/AKT/mTOR signaling pathways in a renal proximal tubular cell line. Additionally, these renoprotective effects were validated in a second model of unilateral ureteral obstruction using a second generation of AD-114 (Fc-fused AD-114, also named AD-214). Collectively, these results suggest a renoprotective role of AD-114 as it inhibited the chemotactic function of CXCR4 as well as blocked CXCR4 downstream p38 MAPK and PI3K/AKT/mTOR signaling, which establish a therapeutic strategy for AD-114 targeting CXCR4 to limit renal fibrosis.

Indexed as

Gene Expression RegulationUp-RegulationAnimalsCell LineDisease Models, AnimalExtracellular MatrixFibrosisHumansKidneyKidney DiseasesMaleMiceMice, Inbred C57BLReceptors, CXCR4Signal TransductionCXCR4 protein, mouseReceptors, CXCR4ChemokinesChronic kidney diseaseFibrosisNephrologyTherapeutics

Identifiers

PMID35015734
PMCPMC8876455
OpenAlexW4205160229

What OpenQuestion holds

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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.