Evidence map›Paper›PMID 34610136›Full record

ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2022

Osteocrin, a bone-derived humoral factor, exerts a renoprotective role in ischemia-reperfusion injury in mice.

Yoshihiko Nishiguchi, Yusuke Hata, Ryosuke Date, Daisuke Fujimoto, Shuro Umemoto, Tomoko Kanki, Hideki Yokoi, Keita P Mori, Takaya Handa, Haruko Watanabe-Takano and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 46% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. The Periosteum in Health and Disease.Current osteoporosis reports · 2025
    Review
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

17 authors at 5 institutions in 1 country.

Yoshihiko NishiguchiDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Yusuke HataDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Ryosuke DateDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Daisuke FujimotoDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Shuro UmemotoDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Tomoko KankiDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Hideki YokoiDepartment of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Keita P MoriDepartment of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Takaya HandaDepartment of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Haruko Watanabe-TakanoDepartment of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
Yugo KanaiDepartment of Diabetes Mellitus and Endocrinology, Osaka Red Cross Hospital, Osaka, Japan.
Akihiro YasodaClinical Research Center, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
Yuichiro IzumiDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Yutaka KakizoeDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Naoki MochizukiDepartment of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
Masashi MukoyamaDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Takashige KuwabaraDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Kumamoto University · JPKyoto University · JPNational Cerebral and Cardiovascular Center · JPKyoto Medical Center · JPOsaka Red Cross Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOsteocrin (OSTN), a bone-derived humoral factor, was reported to act on heart and bone by potentiating the natriuretic peptide (NP) system. Ostn gene polymorphisms have been associated with renal function decline, but its pathophysiological role in the kidney remains unclear.

methodsThe role of endogenous OSTN was investigated using systemic Ostn-knockout (KO) mice. As a model for OSTN administration, liver-specific Ostn-overexpressing mice crossed with KO (KO-Tg) were generated. These mice were subjected to unilateral ischemia-reperfusion injury (IRI) and renal lesions after 21 days of insult were evaluated. A comprehensive analysis of the Wnt/β-catenin pathway was performed using a polymerase chain reaction (PCR) array. Reporter plasmid-transfected proximal tubular cells (NRK52E) were used to investigate the mechanism by which OSTN affects the pathway.

resultsAfter injury, KO mice showed marginal worsening of renal fibrosis compared with wild-type mice, with comparable renal atrophy. KO-Tg mice showed significantly ameliorated renal atrophy, fibrosis and tubular injury, together with reduced expressions of fibrosis- and inflammation-related genes. The PCR array showed that the activation of the Wnt/β-catenin pathway was attenuated in KO-Tg mice. The downstream targets Mmp7, Myc and Axin2 showed similar results. MMP7 and Wnt2 were induced in corticomedullary proximal tubules after injury, but not in KO-Tg. In NRK52E, OSTN significantly potentiated the inhibitory effects of NP on transforming growth factor β1-induced activation of the Wnt/β-catenin pathway, which was reproduced by a cyclic guanosine monophosphate analog.

conclusionsEctopic Ostn overexpression ameliorated subsequent renal injury following ischemia-reperfusion. OSTN could represent possible renoprotection in acute to chronic kidney disease transition, thus serving as a potential therapeutic strategy.

Indexed as

Acute Kidney InjuryMuscle ProteinsRenal Insufficiency, ChronicReperfusion InjuryTranscription FactorsAnimalsFibrosisKidneyMiceMice, Inbred C57BLMice, KnockoutMuscle ProteinsOstn protein, mouseTranscription FactorsAKI to CKDischemia–reperfusionnatriuretic peptidesosteocrinWnt/β-catenin pathway

Identifiers

PMID34610136
PMCPMC8875462
OpenAlexW3204057348

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.