VEGFR3 tyrosine kinase inhibition aggravates cisplatin nephrotoxicity

Author:

Black Laurence M.12ORCID,Farrell Elisa R.12,Barwinska Daria345,Osis Gunars12,Zmijewska Anna A.12,Traylor Amie M.12,Esman Stephanie K.12,Bolisetty Subhashini12,Whipple Grace2,Kamocka Malgorzata M.345,Winfree Seth345,Spangler Daryll R.12,Khan Shehnaz345,Zarjou Abolfazl12,El-Achkar Tarek M.3456ORCID,Agarwal Anupam127ORCID

Affiliation:

1. Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama

2. Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama

3. Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana

4. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana

5. Indiana Center for Biological Microscopy, Indianapolis, Indiana

6. Indianapolis Veterans Affairs Medical Center, Indianapolis, Indiana

7. Birmingham Veterans Administration Medical Center, Birmingham, Alabama

Abstract

Little is known about injury-associated LA in the kidney and its role in the pathophysiology of acute kidney injury (AKI). Observed exacerbation of cisplatin-induced AKI after LA inhibition was accompanied by increased medullary damage and cell death in the kidney. LA inhibition also upregulated compensatory expression of LA regulatory proteins, including JNK and NF-κB. These data support the premise that LA is induced during AKI and lymphatic expansion is a protective mechanism in cisplatin nephrotoxicity.

Funder

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

U.S. Department of Veterans Affairs

Publisher

American Physiological Society

Subject

Physiology

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