Evidence map›Paper›PMID 35451370›Full record

ArticleJCI insight2022

Oxidative stress promotes fibrosis in systemic sclerosis through stabilization of a kinase-phosphatase complex.

Ruiyuan Zhang, Ganesan Senthil Kumar, Uwe Hansen, Martina Zoccheddu, Cristiano Sacchetti, Zachary J Holmes, Megan C Lee, Denise Beckmann, Yutao Wen, Zbigniew Mikulski and 6 more

Open access · goldAbstract read
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 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-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

11 citing papers in PubMed, 12 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

16 authors at 5 institutions in 2 countries.

Ruiyuan ZhangDepartment of Medicine and.
Ganesan Senthil KumarDepartment of Molecular Biology & Biophysics, University of Connecticut Health Center, Farmington, Connecticut, USA.
Uwe HansenInstitute for Musculoskeletal Medicine, University of Munster, Munster, Germany.
Martina ZocchedduDepartment of Medicine and.
Cristiano SacchettiDepartment of Medicine and.
Zachary J HolmesDepartment of Medicine and.
Megan C LeeDepartment of Medicine and.
Denise BeckmannDepartment of Medicine and.
Yutao WenDepartment of Medicine and.
Zbigniew MikulskiMicroscopy and Histology Core Facility, La Jolla Institute for Immunology, La Jolla, California, USA.
Shen YangDepartment of Medicine and.
Eugenio SantelliDepartment of Medicine and.
Rebecca PageDepartment of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut, USA.
Francesco BoinDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Wolfgang PetiDepartment of Molecular Biology & Biophysics, University of Connecticut Health Center, Farmington, Connecticut, USA.
Nunzio BottiniDepartment of Medicine and.
UConn Health · USCedars-Sinai Medical Center · USLa Jolla Institute for Immunology · USUniversity of California San Diego · USUniversity of Münster · DE

Funding

Role of PTP4A1 in systemic sclerosisR01HL151306 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BOTTINI, NUNZIO · 2019 to 2022
$2.4M
NHLBI NIH HHS R01 HL151306
6 · The paper itself

Abstract

Systemic sclerosis (SSc) is a fibrotic autoimmune disease characterized by pathogenic activation of fibroblasts enhanced by local oxidative stress. The tyrosine phosphatase PTP4A1 was identified as a critical promoter of TGF-β signaling in SSc. Oxidative stress is known to functionally inactivate tyrosine phosphatases. Here, we assessed whether oxidation of PTP4A1 modulates its profibrotic action and found that PTP4A1 forms a complex with the kinase SRC in scleroderma fibroblasts, but surprisingly, oxidative stress enhanced rather than reduced PTP4A1's association with SRC and its profibrotic action. Through structural assessment of the oxo-PTP4A1-SRC complex, we unraveled an unexpected mechanism whereby oxidation of a tyrosine phosphatase promotes its function through modification of its protein complex. Considering the importance of oxidative stress in the pathogenesis of SSc and fibrosis, our findings suggest routes for leveraging PTP4A1 oxidation as a potential strategy for developing antifibrotic agents.

Indexed as

Scleroderma, SystemicFibroblastsFibrosisHumansOxidative StressTyrosineTyrosineAutoimmune diseasesFibrosisInflammationRheumatology

Identifiers

PMID35451370
PMCPMC9089796
OpenAlexW4224274102

What Socratic holds

Textmetadata
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 Socratic graph.