Tissue-type plasminogen activator protects against kidney damage in invasive fungal infection.

Authors

Wonseok Choi, Doureradjou Peroumal, Colin T McLaughlin, Kiyoshi P Shiomitsu, Gillian A Moschetta, Kiaan Biswas, Dinubasri Kumariduraivan, Emily Dicesare, Partha S Biswas

Published in

The Journal of experimental medicine. Volume 223. Issue 9. Sep 07, 2026. Epub Jul 21, 2026.

Abstract

Invasive Candida albicans infections (candidiasis) cause progressive organ damage through fungal tissue invasion and toxin-mediated injury, including in the kidney. Hyphal invasion induces apoptosis of renal tubular epithelial cells (RTEC), a key driver of kidney pathology, yet intrinsic renal protective mechanisms remain poorly defined. We identify fibrinolytic tissue-type plasminogen activator (tPA) as a critical mediator of renal tissue protection in candidiasis. tPA is induced by IL-17 and TNFα in renal endothelial cells and RTEC. tPA signals through low-density lipoprotein receptor-related protein 1 (LRP1) and activates ERK1/2 signaling to suppress apoptosis in RTEC. Mice with RTEC-specific deletion of LRP1 exhibited exaggerated kidney damage during candidiasis. Administration of a nonenzymatic form of tPA recapitulated the protective effect of tPA by limiting RTEC apoptosis. These findings reveal the role of tPA/LRP1 axis in preserving renal integrity in candidiasis and suggest clinically approved tPA as a potential therapeutic strategy to mitigate candidiasis-associated tissue injury.

PMID:
42479027
Bibliographic data and abstract were imported from PubMed on 21 Jul 2026.

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