# CD14 in Dahl SS Hypertension and Chronic Kidney Disease

> **NIH NIH F31** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $2,340

## Abstract

Project Summary
Hypertension affects one-third of Americans of which approximately half are termed salt-sensitive. Previous work
in our laboratory has implicated a significant role for the immune system in potentiating the hypertensive and
kidney damage phenotypes which occur in the Dahl Salt-Sensitive (SS) rat. An RNAseq based transcriptomic
experiment on medullary tissue from SS rats fed either a low or high salt diet demonstrated an upregulation of
molecules involved in the innate immune response including Cluster of Differentiation 14 (CD14). CD14 has
been associated with hypertension in various human and animal studies, but mechanistic studies have not been
previously performed. Preliminary studies in SS rats with a genetic knockout of CD14 (SSCD14-/-) show an
exacerbation of the salt-sensitive hypertensive and kidney damage phenotypes. In addition, isolated peritoneal
macrophages from wild type and knockout animals showed an increase ability to produce IL-1β in response to
lipopolysaccharide stimulation in the SSCD14-/-, indicative of a more pro-inflammatory phenotype. This proposal
will address the overall hypothesis that CD14 is a negative regulator of the inflammatory response in
macrophages during development of salt-sensitive hypertension and renal damage. This will be addressed in
two specific aims. Specific Aim 1 test the hypothesis that a null mutation of CD14 will amplify salt-sensitive
hypertension and renal damage in the Dahl SS rat. Experiments in this aim will use SSCD14+/+ and SSCD14-
/- animals on a low- (0.4% NaCl) and high- (4.0%NaCl) salt diet and will assess the development of hypertension
and kidney damage, as well as the number and type of infiltrating immune cells. Specific Aim 2 will interrogate
the function of the altered immune system in the SSCD14-/- animal and will test the hypothesis that CD14
activation is a regulator of macrophage inflammatory phenotype. Infiltrating macrophages will be assessed in
respect to M1/M2 polarization and gene expression patterns.

## Key facts

- **NIH application ID:** 9834684
- **Project number:** 5F31HL144084-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Daniel J Fehrenbach
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,340
- **Award type:** 5
- **Project period:** 2018-12-01 → 2019-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9834684

## Citation

> US National Institutes of Health, RePORTER application 9834684, CD14 in Dahl SS Hypertension and Chronic Kidney Disease (5F31HL144084-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9834684. Licensed CC0.

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