Evidence map›Paper›PMID 40613534›Full record

ArticleActa physiologica (Oxford, England)2025

Lipocalin-2 Restores Soluble Guanylyl Cyclase-Dependent Dilation of the Afferent Arteriole After Renal Transplantation or Ex Vivo Hypoxia/Reoxygenation in Mice.

Liang Zhao, Minze Xu, Anna Maria Pfefferkorn, Cem Erdogan, Hubert Schwelberger, Pinchao Wang, Pratik Hemant Khedkar, Marc Eigen, Falk-Bach Lichtenberger, Rusan Catar and 6 more

Abstract read
In one paragraph

Article in Acta physiologica (Oxford, England), 2025. 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
–field-weighted citation impact
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.

  1. Review
  2. Article
  3. Article
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.

Liang ZhaoInstitute of Translational Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0003-1846-5888
Minze XuInstitute of Translational Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-6169-8495
Anna Maria PfefferkornDepartment of Surgery, Experimental Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-7126-9838
Cem ErdoganInstitute of Translational Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-6319-0978
Hubert SchwelbergerDepartment of Visceral, Transplant and Thoracic Surgery, Medical University Innsbruck, Austria.
Pinchao WangDepartment of Nephrology and Internal Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Pratik Hemant KhedkarInstitute of Translational Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-4778-7731
Marc EigenDepartment of Nephrology and Internal Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Falk-Bach LichtenbergerInstitute of Translational Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-3849-2288
Rusan CatarDepartment of Nephrology and Internal Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
En Yin LaiDepartment of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China.ORCID https://orcid.org/0000-0003-3074-6869
Felix AignerDepartment of Surgery, Experimental Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Pontus B PerssonInstitute of Translational Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Igor Maximilian SauerDepartment of Surgery, Experimental Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Andreas PatzakInstitute of Translational Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-1088-6875
Muhammad Imtiaz AshrafDepartment of Surgery, Experimental Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-6789-5393

Funding

Deutsche ForschungsgemeinschaftZhejiang Provincial Natural Science Foundation of China
6 · The paper itself

Abstract

aimDilatory microvascular function is impaired in ischemia/reperfusion injury in the kidney. Nitric oxide independent activators of soluble guanylyl cyclase (sGC) provide renal protection by dilating microvessels and preserving perfusion, but their efficacy declines after severe hypoxia. This study explores whether lipocalin-2 (Lcn2), a key iron-transporting protein, can restore the sGC-mediated dilation in mouse afferent arterioles (AAs) after hypoxia/reoxygenation (H/R) and kidney transplantation.

methodsDilation of isolated, angiotensin II (Ang II) pre-constricted, AAs was induced by application of sGC activator cinaciguat after pre-constriction with Ang II following H/R (H: 30 min, R: 10 min ± holo-rLcn2, apo-rLcn2, deferoxamine) and syngeneic kidney transplantation (cold ischemia: 30 min or 5.5 h, reperfusion: 20 h ± holo-rLcn2) in C57BL/6 mice. To corroborate the dilatory function at the organ level, vascular relaxation was assessed using an isolated mouse kidney perfusion system.

resultsDilation of AAs was impaired following H/R. Pretreatment with holo-rLcn2 (iron-bound) preserved dilation, whereas apo-rLcn2 (iron-free) had no effect. The reversal of holo-rLcn2's effect by deferoxamine confirmed the role of iron. AAs from kidney transplants showed reduced dilation compared to sham-operated controls, with greater impairment following prolonged ischemia. Treatment with holo-rLcn2 significantly improved dilatory function after extended cold ischemia (5.5 h), restoring it to levels seen with shorter ischemia (30 min). Ex vivo perfusion of the isolated mouse kidney with holo-rLcn2 enhanced cinaciguat-induced vascular relaxation, confirming its beneficial effect at the organ level.

conclusionThis study identifies a novel role for holo-rLcn2 in preserving renal vascular function post-H/R and kidney transplantation, apparently by upholding iron levels in vascular cells.

Indexed as

HypoxiaKidney TransplantationLipocalin-2Reperfusion InjurySoluble Guanylyl CyclaseVasodilationAnimalsArteriolesKidneyMaleMiceMice, Inbred C57BLLcn2 protein, mouseLipocalin-2Soluble Guanylyl Cyclasehypoxia/reoxygenationLipocalin‐2microvascular functionmouse kidney transplantation

Identifiers

PMID40613534
PMCPMC12231162

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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.