Evidence map›Paper›PMID 31081236›Full record

ArticleThe FEBS journal2019

Creation of RANKL mutants with low affinity for decoy receptor OPG and their potential anti-fibrosis activity.

Yizhou Wang, Timo Michiels, Rita Setroikromo, Ronald van Merkerk, Robbert H Cool, Wim J Quax

Open access · hybridAbstract read
In one paragraph

Article in The FEBS journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Delayed denervation-induced muscle atrophy inFrontiers in physiology · 2023
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  5. Article
  6. Review
  7. Article
  8. Article
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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

6 authors at 1 institution in 1 country.

Yizhou WangDepartment of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, The Netherlands.
Timo MichielsDepartment of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, The Netherlands.
Rita SetroikromoDepartment of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, The Netherlands.
Ronald van MerkerkDepartment of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, The Netherlands.
Robbert H CoolDepartment of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, The Netherlands.
Wim J QuaxDepartment of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, The Netherlands.
University of Groningen · NL

Funding

China Scholarship CouncilDutch Top Institute Pharma project TNF-ligands in cancer T3-112Stichting voor de Technische Wetenschappen 11056
6 · The paper itself

Abstract

Fibrosis is characterized by the progressive alteration of the tissue structure due to the excessive production of extracellular matrix (ECM). The signaling system encompassing Receptor Activator of Nuclear factor NF-κB Ligand (RANKL)/RANK/Osteoprotegerin (OPG) was discovered to play an important role in the regulation of ECM formation and degradation in bone tissue. However, whether and how this signaling pathway plays a role in liver or pulmonary ECM degradation is unclear up to now. Interestingly, increased decoy receptor OPG levels are found in fibrotic tissues. We hypothesize that RANKL can stimulate RANK on macrophages and initiate the process of ECM degradation. This process may be inhibited by highly expressed OPG in fibrotic conditions. In this case, RANKL mutants that can bind to RANK without binding to OPG might become promising therapeutic candidates. In this study, we built a structure-based library containing 44 RANKL mutants and found that the Q236 residue of RANKL is important for OPG binding. We show that RANKL_Q236D can activate RAW cells to initiate the process of ECM degradation and is able to escape from the obstruction by exogenous OPG. We propose that the generation of RANKL mutants with reduced affinity for OPG is a promising strategy for the exploration of new therapeutics against fibrosis.

Indexed as

AnimalsExtracellular MatrixFibrosisHumansLiverLungMacrophagesMiceNF-kappa BOsteoprotegerinProtein BindingProtein ConformationRANK LigandReceptor Activator of Nuclear Factor-kappa BSignal TransductionNF-kappa BOsteoprotegerinRANK LigandReceptor Activator of Nuclear Factor-kappa BfibrosisliverlungOPGRANK

Identifiers

PMID31081236
PMCPMC6852375
OpenAlexW2945041648

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.