Shared and Specific miRNA-mRNA in Human and Murine Acute Kidney Injury
Abstract
Acute kidney injury (AKI) is managed as a single clinical entity despite substantial biological heterogeneity. We established a cross-species framework to define etiology-specific molecular programs and determine how these programs relate to molecular heterogeneity and pathobiology in human AKI. We performed parallel sequencing of totalRNA (mRNA) and miRNA (kidney, whole blood) in 3 murine models (mild AKI: ischemia-reperfusion injury, IRI; cecal-ligation and puncture, CLP; endotoxemia, LPS); kidney mRNA and miRNA clearly distinguished the models, blood mRNA maintained model-specific separation, and blood miRNA was less distinct. IRI was characterized by epithelial injury/repair, and extracellular matrix remodeling (i.e., miR-125b-1-3p, Vim, Sprr2g); CLP, broader inflammatory, metabolic programs (i.e., miR-692, Pfkfb3, Cdo1); LPS, inflammatory signaling (i.e., miR-155-5p, Irf7, Gbp3). We then compared these signatures to human whole blood RNAseq. Human blood samples varied along a shared gene axis that correlated to differing degrees with all three murine models, consistent with the heterogeneous nature of clinical AKI rather than discrete assignment to a single experimental etiology. Orthologs were linked to immune processes (i.e., SIGLEC14, DAAM2, CD177, DEFA3), and the presence of tubular casts in human biopsies, reflecting that mild murine AKI models capture etiology-specific biology relevant to severe human AKI. Integration of injury etiology, severity, and time may provide a framework for developing circulating biomarkers that may resolve the biological heterogeneity of human AKI.
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BibTeX
@misc{janosevic2026shared,
title = {{Shared and Specific miRNA-mRNA in Human and Murine Acute Kidney Injury}},
author = {Danielle Janosevic and Thomas W McCarthy and Ashish Sadolikar and Takashi Hato and Michael T Eadon and Pierre Dagher and The Kidney Precision Medicine Project},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.30.762662},
url = {https://www.biorxiv.org/content/10.64898/2026.10.30.762662v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Shared and Specific miRNA-mRNA in Human and Murine Acute Kidney Injury
AU - Danielle Janosevic
AU - Thomas W McCarthy
AU - Ashish Sadolikar
AU - Takashi Hato
AU - Michael T Eadon
AU - Pierre Dagher
AU - The Kidney Precision Medicine Project
PY - 2026
DA - 2026/10/30
PB - bioRxiv
DO - 10.64898/2026.10.30.762662
UR - https://www.biorxiv.org/content/10.64898/2026.10.30.762662v1
AB - Acute kidney injury (AKI) is managed as a single clinical entity despite substantial biological heterogeneity. We established a cross-species framework to define etiology-specific molecular programs and determine how these programs relate to molecular heterogeneity and pathobiology in human AKI. We performed parallel sequencing of totalRNA (mRNA) and miRNA (kidney, whole blood) in 3 murine models (mild AKI: ischemia-reperfusion injury, IRI; cecal-ligation and puncture, CLP; endotoxemia, LPS); kidney mRNA and miRNA clearly distinguished the models, blood mRNA maintained model-specific separation, and blood miRNA was less distinct. IRI was characterized by epithelial injury/repair, and extracellular matrix remodeling (i.e., miR-125b-1-3p, Vim, Sprr2g); CLP, broader inflammatory, metabolic programs (i.e., miR-692, Pfkfb3, Cdo1); LPS, inflammatory signaling (i.e., miR-155-5p, Irf7, Gbp3). We then compared these signatures to human whole blood RNAseq. Human blood samples varied along a shared gene axis that correlated to differing degrees with all three murine models, consistent with the heterogeneous nature of clinical AKI rather than discrete assignment to a single experimental etiology. Orthologs were linked to immune processes (i.e., SIGLEC14, DAAM2, CD177, DEFA3), and the presence of tubular casts in human biopsies, reflecting that mild murine AKI models capture etiology-specific biology relevant to severe human AKI. Integration of injury etiology, severity, and time may provide a framework for developing circulating biomarkers that may resolve the biological heterogeneity of human AKI.
SN - 2692-8205
ER -