Evidence map›Paper›PMID 27209208›Full record

ArticleArthritis research & therapy2016

Knockout of endothelin type B receptor signaling attenuates bleomycin-induced skin sclerosis in mice.

Kengo Akashi, Jun Saegusa, Sho Sendo, Keisuke Nishimura, Takuya Okano, Keiko Yagi, Masashi Yanagisawa, Noriaki Emoto, Akio Morinobu

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

Article in Arthritis research & therapy, 2016. 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
1.7field-weighted citation impact, top 17% 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.

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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

9 authors at 3 institutions in 1 country.

Kengo AkashiDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Jun SaegusaDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Sho SendoDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Keisuke NishimuraDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Takuya OkanoDepartment of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe, Japan.
Keiko YagiDepartment of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe, Japan.
Masashi YanagisawaInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.
Noriaki EmotoDepartment of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe, Japan.
Akio MorinobuDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. morinobu@med.kobe-u.ac.jp.
Kobe University · JPKobe Pharmaceutical University · JPTsukuba International University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEndothelin-1 (ET-1) is important in the pathogenesis of systemic sclerosis (SSc). ET-1 binds two receptors, endothelin type A (ETA) and endothelin type B (ETB). Dual ETA/ETB receptor antagonists and a selective ETA receptor antagonist are used clinically to treat SSc, and the effect of these antagonists on fibroblast activation has been described. However, the role of ETB receptor signaling in fibrogenesis is less clear. This study was conducted to evaluate the profibrotic function of ETB receptor signaling in a murine model of bleomycin (BLM)-induced scleroderma.

methodsWe used ETB receptor-knockout (ETBKO) mice, which are genetically rescued from lethal intestinal aganglionosis by an ETB receptor transgene driven by the human dopamine β-hydroxylase (DβH)-gene promoter, and wild-type mice with DβH-ETB (WT). BLM or phosphate-buffered saline (PBS) was administered subcutaneously by osmotic minipump, and skin fibrosis was assessed by dermal thickness, subcutaneous fat atrophy, and myofibroblast count in the dermis. Dermal fibroblasts isolated from ETBKO and WT mice were cultured in vitro, stimulated with BLM or ET-1, and the expression of profibrotic genes was compared by quantitative PCR.

resultsDermal thickness, subcutaneous fat atrophy, and myofibroblast counts in the dermis were significantly reduced in ETBKO mice compared to WT mice, after BLM treatment. Compared with wild-type, dermal fibroblasts isolated from ETBKO mice showed lower gene expressions of α-smooth muscle actin and collagen 1α1 in response to BLM or ET-1 stimulation in vitro.

conclusionsET-1-ETB receptor signaling is involved in skin sclerosis and in collagen synthesis by dermal fibroblasts.

Indexed as

AnimalsAntibiotics, AntineoplasticBleomycinCollagen Type IDisease Models, AnimalEndothelin-1FibroblastsFibrosisImmunohistochemistryMiceMice, Inbred C57BLMice, KnockoutPolymerase Chain ReactionReceptor, Endothelin BScleroderma, SystemicSignal TransductionAntibiotics, AntineoplasticBleomycinCollagen Type IEDNRB protein, mouseEndothelin-1Receptor, Endothelin BDermal fibroblastEndothelin type B receptorSystemic sclerosis

Identifiers

PMID27209208
PMCPMC4875589
OpenAlexW2403907460

What OpenQuestion holds

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LicenceCC BY
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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.