# Molecular Mechanisms of Renal Injury

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $487,458

## Abstract

Shifts in cellular energy metabolism impact the development and progression of chronic kidney
disease (CKD) through the generation of specific signals that modulate cellular differentiation
and function, cell-cell interactions and inflammation. Perivascular renal interstitial cells and
pericytes support the renal microvasculature and play a critical role in the pathogenesis of CKD.
In kidney injury they represent major cellular sources of myofibroblasts, which promote fibrosis
and the progression of CKD through the pathologic production and deposition of collagen and
other extracellular matrix components in the interstitial space. Perivascular renal interstitial cells
are highly sensitive to changes in tissue pO2 and respond to hypoxia with the production of
erythropoietin, an oxygen-regulated erythropoiesis-stimulating glycoprotein hormone that is
insufficiently produced in patients with CKD. Despite their importance in renal fibrogenesis and
erythropoiesis, perivascular renal interstitial cells are poorly characterized and little is known
about their metabolic functions. Here we hypothesize that shifts in energy metabolism plays a
critical role in the development of renal fibrosis.
Our studies aim at defining the degree of cellular and functional heterogeneity within this
perivascular renal interstitial cell population and at defining the molecular mechanisms that link
cellular energy and mitochondrial metabolism to fibrosis development. Specifically we a)
examine oxygen-regulated metabolism in defined subsets of renal interstitial cells using
temporally controlled conditional gene targeting, b) investigate the role of mitochondrial
metabolism in renal microvascular homeostasis and differentiation and d) to determine to what
degree metabolic reprogramming in perivascular renal interstitial cells impact the development
of renal injury, inflammation and repair.

## Key facts

- **NIH application ID:** 9888374
- **Project number:** 5R01DK081646-12
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Volker Hans Haase
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $487,458
- **Award type:** 5
- **Project period:** 2008-09-18 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888374

## Citation

> US National Institutes of Health, RePORTER application 9888374, Molecular Mechanisms of Renal Injury (5R01DK081646-12). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9888374. Licensed CC0.

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