# MicroRNA In Diabetic Nephropathy

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $460,263

## Abstract

PROJECT SUMMARY/ABSTRACT
We are witnessing a paradigmatic shift in the practice of medicine whereby the concept of targeting RNAs
as diagnostic and therapeutic strategies are rapidly evolving. Lon noncoding RNAs (lncRNAs) are a highly
heterogeneous group of non-coding transcripts that participate in the regulation of almost every stage of gene
expression, as well as being involved in a variety of disease states. Dysregulation of several lncRNAs have
also been implicated in progression of diabetic nephropathy (DN) and because of the tissue-specific
characteristics of lncRNAs, they are considered as the next generation of biomarkers and promising
therapeutic targets for DN progression
 In the last funding cycle, our lab provided strong evidence that lncRNATug1 is down regulated in several
experimental models of DN and in patients with Type 2 diabetes (Long, et al. JCI, 2016). Importantly,
conditional overexpression of Tug1 in podocytes mitigated progression of DN. We also published our findings
demonstrating that Tug1-mediated renoprotection in DN is accomplished through a PGC1a-dependent
mechanisms on mitochondrial function. Thus, we proposed that Tug1 serves as a novel therapeutic target in
DN progression.
 Our work over the last five years suggests that Tug1 has two major effects on mitochondrial function: 1)
Tug1 impacts mitochondrial function indirectly through a PGC1a-dependent mechanism in the nucleus, and 2)
we now provide preliminary data suggesting that Tug1 is also translocated from the nucleus to mitochondria.
However, the impact of mitochondrial-associated Tug1 (mitoTug1) remains unknown. We also provide
preliminary data that Tug1 transcripts localized to the cytoplasm is translated into micropeptides. Several
lncRNAs have been shown to hide small open reading frames (sORFs) encoding for small functional peptides
termed micropeptides. Our preliminary findings suggest a direct effect of Tug1 encoded micropeptide on
mitochondrial function. However, its role on mitochondrial homeostasis and progression of DN is unknown.
 In this application, we propose a convergent model of Tug1-mediated impact on mitochondrial remodeling
in DN. Two fundamental questions will be addressed: 1) First, elucidating the subcellular distribution and
function of mitochondrial-associated Tug1 (mitoTug1) on mitochondrial homeostasis and progression of DN,
and 2) Second, identifying the biological and pathological role of a Tug1-encoded micropepetide on
mitochondrial function and DN progression. We will describe the various techniques and strategies to study the
potential role of Tug1 on mitochondrial remodeling, the challenges to these approaches, and our published and
preliminary data. The successful completion of our application will place high priority on developing strategies
to target Tug1 as a potential candidate in future clinical studies, and open a rich field for investigation on the
interorganelle communication and mitochondrial metabolism in the pathoge...

## Key facts

- **NIH application ID:** 10381348
- **Project number:** 2R01DK091310-12
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** FARHAD R DANESH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $460,263
- **Award type:** 2
- **Project period:** 2011-09-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10381348

## Citation

> US National Institutes of Health, RePORTER application 10381348, MicroRNA In Diabetic Nephropathy (2R01DK091310-12). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10381348. Licensed CC0.

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