Evidence map›Paper›PMID 40209698›Full record

ArticleAmerican journal of nephrology2025

Renal Ischemia Induces Endoplasmic Reticulum Stress and Impairs the Reparative Potency of Scattered Tubular-Like Cells.

Alfonso Eirin, Sara Kazeminia, Barnit Kaur, Kumar Shivam, Xiang-Yang Zhu, Hui Tang, Kyra L Jordan, Shivam Bajpai, Ailing Xue, Alejandro R Chade and 3 more

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Article in American journal of nephrology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

13 authors.

Alfonso Eirin
Sara KazeminiaDivision of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Barnit KaurDivision of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Kumar ShivamDivision of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Xiang-Yang ZhuDivision of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Hui TangDivision of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Kyra L JordanDivision of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Shivam BajpaiDivision of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Ailing XueDivision of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Alejandro R ChadeDepartment of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri, USA.
Maria V IrazabalDivision of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Lilach O LermanDivision of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Alfonso EirinDivision of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Funding

Obesity-induced dysfunction of human MSC in peripheral microvascular repairR01HL158691 · NHLBI · MAYO CLINIC ROCHESTER · PI Alfonso Eirin, Lilach O Lerman · 2022 to 2026
$3.4M
Role of homocysteine metabolism, endothelial function and microvascular rarefaction on renal disease severity and progression in ADPKDR01DK128017 · NIDDK · MAYO CLINIC ROCHESTER · PI IRAZABAL, MARIA V · 2021 to 2024
$2.4M
Role of mitochondrial microRNAs (mitomiRs) in endogenous renal repairR01DK129240 · NIDDK · MAYO CLINIC ROCHESTER · PI Alfonso Eirin · 2023 to 2026
$1.8M
A new large pre-clinical model of aging-related heart failure: a platform to develop new therapies for HFpEFR21AG084154 · NIA · UNIVERSITY OF MISSOURI-COLUMBIA · PI CHADE, ALEJANDRO ROBERTO · 2023 to 2023
$460k
Role of mitochondrial microRNAs (mitomiRs) in endogenous renal repairR56DK129240 · NIDDK · MAYO CLINIC ROCHESTER · PI EIRIN, ALFONSO · 2021 to 2021
$100k
NHLBI NIH HHS R01 HL158691NIA NIH HHS R21 AG084154NIDDK NIH HHS R01 DK128017NIDDK NIH HHS R01 DK129240NIDDK NIH HHS R56 DK129240
6 · The paper itself

Abstract

introductionCD24+/CD133+ scattered tubular-like cells (STCs) are surviving renal cells that acquire progenitor-like characteristics to repair other damaged kidney cells. Renal artery stenosis (RAS) impairs the reparative capacity of STCs, but the underlying mechanisms remain unknown. STCs contain abundant endoplasmic reticulum (ER), but its capacity to fold proteins could become saturated (ER stress), leading to STC dysfunction. We hypothesized that RAS alters the expression of genes implicated in ER stress in swine STCs.

methodsSTCs were harvested from pig kidneys after 10 weeks of RAS or sham (n = 6 each) and expression of ER stress genes was assessed using mRNA-seq (n = 3 each). To elucidate mechanisms regulating ER stress genes in RAS-STCs, integrated mRNA-seq/microRNA (miRNA)-seq and transcription factor (TF) prediction analysis were performed. STC ER stress was assessed in vitro using Western blotting, serial block-face electron microscopy, and mass spectrometry. The involvement of ER stress in regulating the STC-protective effects was also assessed in vitro by their capacity to improve viability of injured human tubular epithelial cells.

resultsRAS pigs developed significant renal dysfunction. mRNA-seq identified 25 ER stress genes upregulated and 30 downregulated in RAS-STCs versus normal-STCs. miRNAs were found to target over a third of all differentially expressed ER stress genes, and almost half of genes encoding for the top 50 TFs involved in regulation of ER stress genes were dysregulated in RAS-STCs. RAS-STCs exhibited higher ER stress compared to normal-STCs, reflected in significant ER dilation and formation of ER-mitochondria contacts and increased levels of ER stress-related amino acids. Importantly, ER stress inhibition improved the reparative capacity of RAS-STCs in vitro.

conclusionRenal ischemia alters expression of ER stress-related genes in swine STCs, likely through post-transcriptional- and TF-regulatory mechanisms, which induces ER stress and impairs their reparative potency. These alterations may limit the potential of STCs to repair damaged kidneys in subjects with RAS.

Indexed as

Endoplasmic Reticulum StressIschemiaKidney TubulesRenal Artery ObstructionAnimalsDisease Models, AnimalHumansKidneyMicroRNAsSwineMicroRNAsEndoplasmic reticulum stressMicroRNAmRNARenal ischemiaScattered tubular-like cells

Identifiers

PMID40209698
PMCPMC12353061

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