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Updated: Jun 24, 2026
Detection of MicroRNA Expression in the Kidneys of Immunoglobulin A Nephropathic Mice
Published on: July 8, 2020
MicroRNA expression profiles predictive of human renal allograft status
Dany Anglicheau1, Vijay K Sharma, Ruchuang Ding
1Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian-Weill Cornell Medical Center, New York, NY 10065, USA.
Abstract:
Immune rejection of organ transplants is a life-threatening complication and is exemplified by alterations in the expression of protein-encoding genes. Because microRNAs (miRNAs) regulate the expression of genes implicated in adaptive immunity, we investigated whether acute rejection (AR) is associated with alterations in miRNA expression within allografts and whether expression profiles are diagnostic of AR and predict allograft function. Seven of 33 renal allograft biopsies (12 AR and 21 normal) were profiled using microfluidic cards containing 365 mature human miRNAs (training set), and a subset of differentially expressed miRNAs were quantified in the remaining 26 allograft biopsies (validation set). We found a strong association between intragraft expression of miRNAs and messenger RNAs (mRNAs), and that AR, and renal allograft function, could be predicted with a high level of precision using intragraft levels of miRNAs. Our investigation of miRNA expression in normal human peripheral blood mononuclear cells (PBMCs) showed that miRNAs (miR-142-5p, -155, and -223) overexpressed in AR biopsies are highly expressed in PBMCs, and that stimulation with the mitogen phytohaemagglutinin results in an increase in the abundance of miR-155 and a decrease in miR-223 and let-7c. Quantification of miRNAs in primary cultures of human renal epithelial cells (HRECs) showed that miR-30a-3p, -10b, and let-7c are highly expressed in HRECs, and that stimulation results in a decreased expression of miR-30a-3p. Our studies, in addition to suggesting a cellular basis for the altered intragraft expression of miRNAs, propose that miRNA expression patterns may serve as biomarkers of human renal allograft status.
Insights
Acute rejection in organ transplants is linked to changes in microRNA (miRNA) expression within allografts. Intragraft miRNA levels can accurately predict rejection and allograft function, suggesting their potential as diagnostic biomarkers.
Area of Science:
- Transplant immunology
- Molecular biology
- Biomarker discovery
Background:
- Organ transplant rejection is a major clinical challenge.
- Gene expression changes, including microRNAs (miRNAs), are implicated in transplant rejection.
- miRNAs play a crucial role in regulating adaptive immunity.
Purpose of the Study:
- To investigate alterations in miRNA expression during acute rejection (AR) of renal allografts.
- To determine if miRNA expression profiles can diagnose AR and predict allograft function.
- To explore the cellular origins of altered intragraft miRNA expression.
Main Methods:
- Microfluidic cards profiling 365 human miRNAs in renal allograft biopsies (training and validation sets).
- Quantification of specific miRNAs in peripheral blood mononuclear cells (PBMCs) and human renal epithelial cells (HRECs).
- Analysis of miRNA and messenger RNA (mRNA) expression associations.
Main Results:
- A strong correlation was found between intragraft miRNA and mRNA expression.
- Intragraft miRNA levels accurately predicted AR and allograft function.
- Specific miRNAs (miR-142-5p, -155, -223) overexpressed in AR biopsies are also found in PBMCs.
- Stimulation of PBMCs and HRECs altered the expression of certain miRNAs.
Conclusions:
- Altered intragraft miRNA expression is associated with acute renal allograft rejection.
- miRNA expression patterns show promise as non-invasive biomarkers for monitoring allograft status.
- The study suggests a cellular basis for observed miRNA expression changes in allografts.
