DPP4 inhibition mitigates ANG II-mediated kidney immune activation and injury in male mice

Author:

Nistala Ravi123ORCID,Meuth Alex I.234,Smith Cassandra235,An Jianzhong123,Habibi Javad235,Hayden M. R.235,Johnson Megan25,Aroor Annayya235,Whaley-Connell Adam123,Sowers James R.2356,McKarns Susan C.7,Bender Shawn B.346ORCID

Affiliation:

1. Divisions of Nephrology and Hypertension, University of Missouri School of Medicine, Columbia, Missouri

2. Diabetes and Cardiovascular Center, University of Missouri School of Medicine, Columbia, Missouri

3. Department of Research, Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri

4. Department of Biomedical Sciences, University of Missouri, Columbia, Missouri

5. Divisions of Endocrinology and Metabolism, Department of Medicine, University of Missouri School of Medicine, Columbia, Missouri

6. Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri

7. Departments of Microbiology and Immunology and Surgery, University of Missouri School of Medicine, Columbia, Missouri

Abstract

This work highlights the role of dipeptidyl peptidase-4 (DPP4) in promoting ANG II-mediated kidney inflammation and injury. Specifically, ANG II infusion in mice led to increases in blood pressure and kidney DPP4 activity, which then led to activation of CD8+ T cells, Ly6C macrophages, and neutrophils and suppression of anti-inflammatory T helper 2 lymphocytes and regulatory T cells. Collectively, this led to kidney injury, characterized by mesangial expansion, mitochondrial damage, and albuminuria, which were mitigated by DPP4 inhibition independent of blood pressure reduction.

Funder

Biomedical Laboratory Research and Development, VA Office of Research and Development

HHS | NIH | National Heart, Lung, and Blood Institute

HHS | NIH | National Institute of Environmental Health Sciences

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

American Physiological Society

Subject

Physiology

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