Evidence mapPaperPMID 41846397Full record

ArticleJournal of cachexia, sarcopenia and muscle2026

IL-15 Links Muscle-Kidney Crosstalk to Preserving Podocyte Mitochondrial Fusion and Attenuating Diabetic Nephropathy.

Yin Li, Jialing Rao, Weiyan Lai, Yuxiang Sun, Hongchun Lin, Jun Zhang, Zengchun Ye, Zhaoyong Hu, Hui Peng

Abstract read
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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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.

Yin LiNephrology Division, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Jialing RaoNephrology Division, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Weiyan LaiNephrology Division, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Yuxiang SunNephrology Division, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Hongchun LinNephrology Division, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Jun ZhangNephrology Division, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Zengchun YeNephrology Division, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Zhaoyong HuNephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Hui PengNephrology Division, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.ORCID https://orcid.org/0000-0002-0220-3616

Funding

PROTEIN NUTRITION IN EXPERIMENTAL UREMIAR01DK037175 · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · 1986 to 2025
$1.8M
Basic and Applied Basic Research Foundation of Guangzhou, China 2023A04J1805Guangdong Provincial Enterprise Joint Fund-Key projects 2021B1515230005National Natural Science Foundation of China 81873613National Natural Science Foundation of China 82000727NIDDK NIH HHS R01 DK037175NIH HHS 5R01DK037175
6 · The paper itself

Abstract

objectivesHigh glucose induces mitochondrial dysfunction in podocytes, contributing to the development of diabetic nephropathy (DN). There is increasing evidence that muscles play a protective role by secreting myokines into the kidneys. Here, we investigated how skeletal muscle influences podocyte health via muscle-kidney crosstalk.

methodsTo increase myokine release, we overexpressed PGC-1α specifically in skeletal muscle (mPGC-1α) and crossed these mice with db/m mice to generate diabetic mPGC-1α:db/db mice. In parallel, db/db mice were treated intraperitoneally with recombinant murine interleukin-15 (IL-15). Mechanistic studies were performed using isolated primary podocytes and cultured podocyte cell lines.

resultsCompared with db/db controls, mPGC-1α:db/db mice exhibited reduced urinary albumin excretion (p < 0.001), mesangial matrix expansion (p < 0.001), glomerular basement membrane thickening (p < 0.001) and urinary podocin excretion (p < 0.001), along with increased podocyte number (p < 0.001). Podocytes from mPGC-1α:db/db mice showed higher expression of Nephrin and COX IV (p < 0.05) and upregulation of multiple mitochondrial function-related genes, notably OPA1 (p < 0.05). Skeletal muscle from mPGC-1α:db/db mice displayed elevated IL-15 mRNA (p < 0.05) and protein (p < 0.01) levels, accompanied by increased plasma IL-15 concentrations (p < 0.05). IL-15 treatment enhanced podocyte mitochondrial respiration, including basal oxygen consumption rate (OCR, p < 0.05), ATP-coupled respiration (p < 0.05) and maximal respiration (p < 0.05). IL-15 preserved mitochondrial fusion under high-glucose conditions by increasing OPA1 expression (p < 0.05) and promoted OPA1 transcription via histone H3 acetylation at its promoter (p < 0.05).

conclusionsSkeletal muscle-derived IL-15 mediates renal protection by maintaining mitochondrial fusion in podocytes during DN progression. Targeting this pathway may offer a therapeutic strategy to preserve kidney function and slow progression to end-stage renal disease.

Indexed as

Diabetic NephropathiesInterleukin-15KidneyMitochondrial DynamicsMuscle, SkeletalPodocytesAnimalsMaleMiceMyokinesPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaInterleukin-15MyokinesPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphadiabetic nephropathyinterleukin‐15mitochondriaoptic atrophy 1podocyte

Identifiers

PMID41846397
PMCPMC13140195

What Socratic holds

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LicenceCC BY
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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 Socratic graph.