# Targeting MicroRNA miR-122 for the Treatment of Perioperative Liver Injury

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $450,014

## Abstract

PROJECT SUMMARY
The goal of this proposal is to identify microRNA (miRNA) targets as innovative therapeutic approach for the
treatment of hepatic ischemia and reperfusion injury. Hepatic ischemia and reperfusion injury is a significant
source of morbidity and mortality during major hepatic resection and during liver transplantation. MiRNAs
constitute a family of noncoding RNA molecules of 20 to 25 nucleotides in length that regulate gene expression
at the posttranscriptional level. In order to identify functionally important miRNAs during hepatic ischemia and
reperfusion, we performed a targeted miRNA screen in a murine model of liver ischemia. We observed the
most dramatic increase in miRNA expression for miR-122 – a liver-specific miRNA that is functionally
implicated in the propagation of the hepatitis C virus. Subsequent studies of hepatic ischemia and reperfusion
injury in mice with hepatocyte-specific deletion of miR-122 revealed dramatic increases in hepatic tissue injury.
Utilization of a hepatocyte cell line with lentiviral-mediated overexpression of miR-122 allowed us to identify the
oxygen-sensing prolyl-hydroxylase PHD1 as a novel target gene for miR-122. Thus, we hypothesize that
HIF1A-dependent induction of miR-122 represents a feed-forward pathway for liver protection that enhances
hypoxia-elicited liver protection via repression of its target gene PHD1.

## Key facts

- **NIH application ID:** 10366015
- **Project number:** 5R01DK122796-03
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Holger K. Eltzschig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $450,014
- **Award type:** 5
- **Project period:** 2020-05-11 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10366015

## Citation

> US National Institutes of Health, RePORTER application 10366015, Targeting MicroRNA miR-122 for the Treatment of Perioperative Liver Injury (5R01DK122796-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10366015. Licensed CC0.

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