# Role of mitochondrial microRNAs (mitomiRs) in endogenous renal repair

> **NIH NIH R56** · MAYO CLINIC ROCHESTER · 2021 · $100,000

## Abstract

Renal artery stenosis (RAS) remains a common cause of hypertension and end-stage renal disease in the
elderly population, associated with increased morbidity and mortality. Recent data suggest that renal ischemia
in RAS interferes with endogenous kidney repair mechanisms, such as CD133+/CD24+ scattered tubular-like
cells (STCs), which can proliferate and their progeny re-differentiate into tubular epithelial cells to replace lost
neighboring injured tubular cells. Our previous studies have shown that experimental RAS impairs the
reparative capacity of swine STCs by inducing structural and functional abnormalities in their mitochondria.
However, the processes underpinning RAS-induced STC mitochondrial damage remain unclear.
 Micro-RNAs (miRNAs) are non-coding RNA fragments that function as post-transcriptional regulators of
gene expression. MiRNA genes are transcribed in the nucleus, which results in the production of pri- and pre-
miRNA precursors, and subsequently mature miRNAs. Although most mature miRNAs are present in the
cytosol, few miRNAs, known as ‘mitomiRs’, translocate to the mitochondrion to silence gene expression related
to mitochondrial functions.
 Our preliminary data show that RAS increases expression of mitomiRs in swine STCs, associated with
decreased expression of mitochondrial DNA (mtDNA) genes, and in turn mitochondrial structural abnormalities
and dysfunction. Our pilot experiments also show that the promoters and enhancers of mitomiRs exhibit hyper
5-hydroxymethylation of cytosine (5hmC), an epigenetic mark generated by the oxidation of 5mC by the ten-
eleven translocation methylcytosine dioxygenase (TET). Possibly, renal ischemia in RAS may alter mitomiR
biogenesis and interfere with mitochondrial function in STCs. This might be partly mediated by epigenetic
processes (5hmC) within mitomiR regulatory regions and/or increased import of mitomiRs into mitochondria.
The working hypothesis underlying this proposal is that altered mitomiR expression in STCs underlies
RAS-induced STC mitochondrial damage, blunting the paracrine function and capacity of STCs to
preserve the post-stenotic kidney. Three specific aims will be pursued: Aim 1: will test whether increased
mitomiR expression in RAS-STCs induces mitochondrial structural damage and dysfunction in STCs. Aim 2:
will test whether RAS imposes epigenetic changes that increase mitomiR expression in STCs. Aim 3: will test
whether aberrant mitomiR mitochondrial import contributes to STC dysfunction. Successful studies will provide
novel insight into the vulnerability of this repair system and may contribute towards development of feasible
clinically relevant tools for improving the utility and efficacy of kidney repair in renal disease.

## Key facts

- **NIH application ID:** 10471652
- **Project number:** 1R56DK129240-01
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Alfonso Eirin
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $100,000
- **Award type:** 1
- **Project period:** 2021-09-17 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471652

## Citation

> US National Institutes of Health, RePORTER application 10471652, Role of mitochondrial microRNAs (mitomiRs) in endogenous renal repair (1R56DK129240-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10471652. Licensed CC0.

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