Evidence map›Paper›PMID 34103333›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2021

Kidney-Targeted Delivery of Prolyl Hydroxylase Domain Protein 2 Small Interfering RNA with Nanoparticles Alleviated Renal Ischemia/Reperfusion Injury.

Dengpiao Xie, Juan Wang, Gaizun Hu, Chaoling Chen, Hu Yang, Joseph K Ritter, Yun Qu, Ningjun Li

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.1field-weighted citation impact, top 25% 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

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
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  6. Nanotherapeutics in Kidney Disease: Innovations, Challenges, and Future Directions.Journal of the American Society of Nephrology : JASN · 2025
    Review
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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

8 authors at 3 institutions in 2 countries.

Dengpiao XieDepartment of Pharmacology & Toxicology, Virginia Commonwealth University School of Medicine, Richmond, Virginia (D.X., G.H., C.C., J.K.R., N.L.); College of Biomedical Engineering, Sichuan University, Chengdu, China (J.W.); Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri (H.Y.); and Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia (Y.Q.).
Juan WangDepartment of Pharmacology & Toxicology, Virginia Commonwealth University School of Medicine, Richmond, Virginia (D.X., G.H., C.C., J.K.R., N.L.); College of Biomedical Engineering, Sichuan University, Chengdu, China (J.W.); Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri (H.Y.); and Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia (Y.Q.).
Gaizun HuDepartment of Pharmacology & Toxicology, Virginia Commonwealth University School of Medicine, Richmond, Virginia (D.X., G.H., C.C., J.K.R., N.L.); College of Biomedical Engineering, Sichuan University, Chengdu, China (J.W.); Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri (H.Y.); and Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia (Y.Q.).
Chaoling ChenDepartment of Pharmacology & Toxicology, Virginia Commonwealth University School of Medicine, Richmond, Virginia (D.X., G.H., C.C., J.K.R., N.L.); College of Biomedical Engineering, Sichuan University, Chengdu, China (J.W.); Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri (H.Y.); and Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia (Y.Q.).
Hu YangDepartment of Pharmacology & Toxicology, Virginia Commonwealth University School of Medicine, Richmond, Virginia (D.X., G.H., C.C., J.K.R., N.L.); College of Biomedical Engineering, Sichuan University, Chengdu, China (J.W.); Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri (H.Y.); and Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia (Y.Q.).
Joseph K RitterDepartment of Pharmacology & Toxicology, Virginia Commonwealth University School of Medicine, Richmond, Virginia (D.X., G.H., C.C., J.K.R., N.L.); College of Biomedical Engineering, Sichuan University, Chengdu, China (J.W.); Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri (H.Y.); and Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia (Y.Q.).
Yun QuDepartment of Pharmacology & Toxicology, Virginia Commonwealth University School of Medicine, Richmond, Virginia (D.X., G.H., C.C., J.K.R., N.L.); College of Biomedical Engineering, Sichuan University, Chengdu, China (J.W.); Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri (H.Y.); and Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia (Y.Q.).
Ningjun LiDepartment of Pharmacology & Toxicology, Virginia Commonwealth University School of Medicine, Richmond, Virginia (D.X., G.H., C.C., J.K.R., N.L.); College of Biomedical Engineering, Sichuan University, Chengdu, China (J.W.); Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri (H.Y.); and Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia (Y.Q.) nli@vcu.edu.
Virginia Commonwealth University · USSichuan University · CNMissouri University of Science and Technology · US

Funding

Renal Medullary HIF Prolyl Hydroxylases and Salt Sensitivity of Blood PressureR01HL089563 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, NINGJUN · 2007 to 2016
$3.4M
Modulating Macrophage Function in Atherosclerosis by Functionalized NanoparticlesR01HL140684 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GHOSH, SIDDHARTHA S, YANG, HU · 2018 to 2021
$2.5M
Renal sphingosine-1-phosphate receptor 1 in salt-sensitive hypertensionR01HL145163 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, NINGJUN · 2019 to 2022
$1.6M
Renal Medullary Stem Cell Niche in Salt Sensitive HypertensionR01HL106042 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, NINGJUN · 2011 to 2014
$1.5M
Renomedullary metabolism of anandamide and blood pressure regulationR01DK102539 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN, RITTER, JOSEPH K. · 2016 to 2019
$1.4M
Molecular mechanism of hypertension-induced renal injury: the role of HIF-1alphaR01DK107991 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, NINGJUN · 2017 to 2019
$698k
Renomedullary metabolism of anandamide and blood pressure regulationR56DK102539 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN, RITTER, JOSEPH K. · 2014 to 2014
$92k
NHLBI NIH HHS R01 HL089563NHLBI NIH HHS R01 HL106042NHLBI NIH HHS R01 HL140684NHLBI NIH HHS R01 HL145163NIDDK NIH HHS R01 DK102539NIDDK NIH HHS R01 DK107991NIDDK NIH HHS R56 DK102539
6 · The paper itself

Abstract

Inhibition of hypoxia-inducible factor-prolyl hydroxylase (PHD) has been shown to protect against various kidney diseases. However, there are controversial reports on the effect of PHD inhibition in renoprotection. The present study determined whether delivery of PHD2 small interfering RNA (siRNA) using an siRNA carrier, folic acid (FA)-decorated polyamidoamine dendrimer generation 5 (G5-FA), would mainly target kidneys and protect against renal ischemia/reperfusion injury (I/R). The renal I/R was generated by clipping the renal pedicle for 30 minutes in uninephrectomized mice. Mice were sacrificed 48 hours after I/R. Normal saline or G5-FA complexed with control or PHD2 siRNA was injected via tail vein 24 hours before ischemia. After the injection of near-infrared fluorescent dye-labeled G5-FA, the fluorescence was mainly detected in kidneys but not in other organs. The reduction of PHD2 mRNA and protein was only observed in kidneys but not in other organs after injection of PHD2-siRNA-G5-FA complex. The injection of PHD2-siRNA-G5-FA significantly alleviated renal I/R injury, as shown by the inhibition of increases in serum creatinine and blood urea nitrogen, the blockade of increases in kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, and the improvement of histologic damage compared with mice treated with control siRNA. PHD2 siRNA can be delivered specifically into kidneys using G5-FA, and that local knockdown of PHD2 gene expression within the kidney alleviates renal I/R injury. Therefore, G5-FA is an efficient siRNA carrier to deliver siRNA into the kidney, and that local inhibition of PHD2 within the kidney may be a potential strategy for the management of acute I/R injury. SIGNIFICANCE STATEMENT: Folic acid (FA)-decorated polyamidoamine dendrimer generation 5 (G5-FA) was demonstrated to be an effective carrier to deliver small interfering RNA (siRNA) into kidneys. Delivery of prolyl hydroxylase domain protein 2 siRNA with G5-FA effectively protected the kidneys against the acute renal ischemia/reperfusion injury.

Indexed as

Hypoxia-Inducible Factor-Proline DioxygenasesKidneyNanoparticlesReperfusion InjuryRNA, Small InterferingAnimalsDendrimersFolic AcidMaleMiceMice, Inbred C57BLDendrimersEgln1 protein, mouseFolic AcidHypoxia-Inducible Factor-Proline DioxygenasesRNA, Small Interfering

Identifiers

PMID34103333
PMCPMC11047054
OpenAlexW3170662375

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.