# Post-transcriptional regulation of gene expression by microRNAs in antibody-mediated rejection

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 2022 · $701,088

## Abstract

Chronic antibody-mediated rejection (AMR) is a major cause of renal allograft rejection. Yet
despite its clinical importance an integrated understanding of how responses to antibody and
complement mediated attack are regulated by the transplanted kidney has not been established.
This gap in our knowledge is due at least in part to an incomplete understanding of responses
made by the kidney that result in gene regulation promote or prevent injury. MicroRNAs (miRNAs)
are a class of small noncoding RNAs that regulate gene expression post-transcriptionally.
miRNAs play an important role in regulating renal injury. However, the study of miRNAs in
rejection and renal injury has largely been based on analysis of total cellular miRNAs that are
differentially expressed during disease. This approach is problematic because it does not provide
information on the mRNAs targeted by these miRNAs. To address this issue, we asked whether
it is possible to isolate miRNAs and the mRNAs they are targeting in the RNA-Induced Silencing
Complex (RISC) by isolating RNAs cross-linked to the RNA Binding Protein (RBP) AGO2. Using
this approach we defined the first miRNA-mRNA interaction map for transplant related renal injury.
These proof-of-principle studies revealed that within the miRNA-mRNA targetome it is possible to
defined miRNAs and the mRNAs they target that undergo unique changes in cells undergoing
injury. Pathway enrichment analysis indicated that miRNAs present in the RISC complex target
mRNAs encoding proteins in pathways that may contribute to injury. Based on these studies, we
hypothesize that the miRNA-mRNA targetome can be used to identify gene pathways that
contribute to AMR. To test this hypothesis, we will use a clinically relevant murine model to
determine the miRNA-mRNA map for AMR and use information elucidated by the targetome to
examine gene pathways under regulation by miRNAs. We examine the clinical relevance of our
findings by examining whether similar changes occur in human kidney transplants. These studies
will provide unique insight into process that drive pathology associated with AMR, information that
could be used to distinguish AMR from other types of injury, and provides a novel resource to the
transplantation and wider scientific community.

## Key facts

- **NIH application ID:** 10522285
- **Project number:** 1R01DK131204-01A1
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Robert L Fairchild
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $701,088
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522285

## Citation

> US National Institutes of Health, RePORTER application 10522285, Post-transcriptional regulation of gene expression by microRNAs in antibody-mediated rejection (1R01DK131204-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10522285. Licensed CC0.

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