# The role of microRNAs in progressive renal decline in Type 1 diabetes

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $352,775

## Abstract

PROJECT SUMMARY
 Progressive renal decline is the central manifestation of diabetic nephropathy (DN) that leads to end-stage
renal disease (ESRD). In participants of the Joslin Kidney Study (JKS), a longitudinal investigation of the
natural history of DN in Type 1 diabetes (T1D), we recently demonstrated that microRNAs (miRNAs) involved
in transforming growth factor (TGF)-β1 mediated renal fibrogenesis are deregulated early in patients who are
at risk for progression to ESRD. Importantly, this deregulation occurs prior to the initiation of renal function
decline, suggesting that these miRNAs have potential utility as novel biomarkers of the risk of progression to
ESRD in DN. We hypothesize that additional miRNAs exist that play important roles in renal function decline in
patients who are at risk of progression to ESRD but have not yet been studied. The identification of these
miRNAs will lead to the discovery of novel factors involved in the pathogenesis of renal function decline.
 The goals of the proposed research project is to further leverage biobanked specimens from the JKS,
along with innovative next-generation sequencing technology, to i) determine the expression profile of the full
complement of miRNAs that are differentially expressed early in T1D patients who are at risk for progression to
ESRD and prior to the initiation of renal function decline and ii) to begin to investigate the mechanisms by
which these miRNAs contribute to disease pathogenesis.
 These goals will be accomplished through three Specific Aims. 1) To establish a comprehensive set of
candidate miRNAs for early renal function decline. We will i) apply next-generation sequencing technology
(miRNA-Seq) to assess miRNA levels in baseline plasma specimens from 80 non-progressors and 80 rapid
progressors from the JKS and ii) define a set of candidate miRNAs for early renal function decline in T1D using
robust statistical methodologies. 2) To validate the candidate miRNAs and examine their expression in
additional T1D patients with early renal function decline. We will i) perform cross-platform validation (qPCR) of
the candidate miRNAs identified in Aim 1 in all 80 non-progressors and 80 rapid progressors and ii) validate
these miRNAs in 159 additional non-progressors and rapid progressors from the JKS. 3) To identify the
miRNA:target interactions that are altered in early renal function decline. We will i) identify the biologically
significant targets of the top-ranked differentially expressed candidate miRNAs identified in Aim 2 and ii)
experimentally validate and functionally assess these miRNA:target interactions. Our approach is highly
innovative and involves a multidisciplinary team of investigators with expertise in all aspects of the proposed
research. Our implementation of this study will define currently unknown factors in DN and may lead to the
identification of novel therapeutic targets to prevent progression of renal decline in T1D.

## Key facts

- **NIH application ID:** 9934187
- **Project number:** 5R01DK110350-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Marcus Guy Pezzolesi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,775
- **Award type:** 5
- **Project period:** 2017-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934187

## Citation

> US National Institutes of Health, RePORTER application 9934187, The role of microRNAs in progressive renal decline in Type 1 diabetes (5R01DK110350-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934187. Licensed CC0.

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