VEGFR3 tyrosine kinase inhibition aggravates cisplatin nephrotoxicity
Laurence M. Black, Elisa R. Farrell, Daria Barwinska, Gunars Osis, Anna A. Zmijewska, Amie Traylor, Stephanie K. Esman, Subhashini Bolisetty, Grace Whipple, Malgorzata M. Kamocka, Seth Winfree, Daryll Spangler, Shehnaz Khan, Abolfazl Zarjou, Tarek M. El‐Achkar, Anupam Agarwal
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.