Evidence map›Paper›PMID 31846485›Full record

ArticlePloS one2019

Tyrphostin AG490 reduces inflammation and fibrosis in neonatal obstructive nephropathy.

Mojca Gasparitsch, Alexandra Schieber, Teresa Schaubeck, Ursula Keller, Marco Cattaruzza, Bärbel Lange-Sperandio

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. 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
1.2field-weighted citation impact, top 18% 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, 18 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

6 authors at 2 institutions in 1 country.

Mojca GasparitschDr. v. Hauner Children's Hospital, Division of Pediatric Nephrology, Ludwig-Maximilians-University, Munich, Germany.
Alexandra SchieberDr. v. Hauner Children's Hospital, Division of Pediatric Nephrology, Ludwig-Maximilians-University, Munich, Germany.
Teresa SchaubeckDr. v. Hauner Children's Hospital, Division of Pediatric Nephrology, Ludwig-Maximilians-University, Munich, Germany.
Ursula KellerDr. v. Hauner Children's Hospital, Division of Pediatric Nephrology, Ludwig-Maximilians-University, Munich, Germany.
Marco CattaruzzaDepartment of Physiology, Ruprecht-Karls-University, Heidelberg, Germany.
Bärbel Lange-SperandioDr. v. Hauner Children's Hospital, Division of Pediatric Nephrology, Ludwig-Maximilians-University, Munich, Germany.ORCID 0000-0001-8898-3459
Ludwig-Maximilians-Universität München · DEHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCongenital obstructive nephropathy is the main cause of end-stage renal disease in infants and children. Renal insufficiency is due to impaired growth and maturation in the developing kidney with obstruction. Congenital obstructive nephropathy leads to cytokine mediated inflammation and the development of interstitial fibrosis. The Janus kinase-2 (JAK-2) and Signal Transducer and Activator of Transcription'-3 (STAT3) are involved in cytokine production, inflammation, and interstitial fibrosis.

methodsWe studied the role of JAK2/STAT3 in a model of congenital obstructive nephropathy using unilateral ureteral obstruction (UUO) in neonatal mice at the second day of life. Cytokine production, inflammation, and interstitial fibrosis were analyzed in obstructed and sham operated kidneys of neonatal mice treated with or without JAK2/STAT3 inhibitor Tyrphostin AG490. To mimic obstruction and distension, proximal tubular cells were stretched in vitro.

resultsWe show that STAT3 is highly activated in the developing kidney with obstruction and in proximal tubular cells following stretch. JAK2/STAT3 activation mediates cytokine release and leukocyte recruitment into neonatal kidneys after UUO. Pharmacological blockade of JAK2/STAT3 by Tyrphostin AG490 reduced inflammation, tubular apoptosis, and interstitial fibrosis. JAK2/STAT3 blockade decreased pro-inflammatory and profibrotic mediators in tubular cells.

conclusionOur findings provide evidence that JAK2/STAT3 mediates inflammation and fibrosis in the developing kidney with obstruction. Blocking JAK2/STAT3 may prove beneficial in congenital obstructive nephropathy in children.

Indexed as

AnimalsAnimals, NewbornEnzyme InhibitorsFibrosisInflammationJanus Kinase 2MiceSTAT3 Transcription FactorTyrphostinsUreteral Obstructionalpha-cyano-(3,4-dihydroxy)-N-benzylcinnamideEnzyme InhibitorsJak2 protein, mouseJanus Kinase 2Stat3 protein, mouseSTAT3 Transcription FactorTyrphostins

Identifiers

PMID31846485
PMCPMC6917291
OpenAlexW2994733649

What OpenQuestion holds

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Registered trials

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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.