Research output per year
Research output per year
Fan Yang, Elyce Ozols, Frank Y. Ma, Khai Gene Leong, Greg H. Tesch, Xiaoyun Jiang, David J. Nikolic-Paterson
Research output: Contribution to journal › Article › Research › peer-review
Aristolochic acid (AA) is a toxin that induces DNA damage in tubular epithelial cells of the kidney and is the cause of Balkan Nephropathy and Chinese Herb Nephropathy. In cultured tubular epithelial cells, AA induces a pro-fibrotic response via the c-Jun amino terminal kinase (JNK) signaling pathway. This study investigated the in vivo role of JNK signaling with a JNK inhibitor (CC-930) in mouse models of acute high dose AA-induced kidney injury (day 3) and renal fibrosis induced by chronic low dose AA exposure (day 22). CC-930 treatment inhibited JNK signaling and protected from acute AA-induced renal function impairment and severe tubular cell damage on day 3, with reduced macrophage infiltration and expression of pro-inflammatory molecules. In the chronic model, CC-930 treatment inhibited JNK signaling but did not affect AA-induced renal function impairment, tubular cell damage including the DNA damage response and induction of senescence, or renal fibrosis; despite a reduction in the macrophage pro-inflammatory response. In conclusion, JNK signaling contributes to acute high dose AA-induced tubular cell damage, presumably via an oxidative stress-dependent mechanism, but is not involved in tubular atrophy and senescence that promote chronic kidney disease caused by ongoing DNA damage in chronic low dose AA exposure.
Original language | English |
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Article number | 599114 |
Number of pages | 12 |
Journal | Frontiers in Physiology |
Volume | 12 |
DOIs | |
Publication status | Published - 12 Feb 2021 |
Research output: Contribution to journal › Comment / Debate › Other › peer-review
National Health and Medical Research Council (NHMRC) (Australia)
1/01/09 → 31/12/19
Project: Research