TAK1 deficiency attenuates cisplatin-induced acute kidney injury.
Jun ZhouChanglong AnXiaogao JinZhaoyong HuRobert L SafirsteinYanlin WangPublished in: American journal of physiology. Renal physiology (2019)
Cisplatin can cause acute kidney injury (AKI), but the molecular mechanisms are not well understood. The objective of the present study was to examine the role of transforming growth factor-β-activated kinase-1 (TAK1) in the pathogenesis of cisplatin-induced AKI. Wild-type mice and proximal tubule TAK1-deficient mice were treated with vehicle or cisplatin. Compared with wild-type control mice, proximal tubule TAK1-deficient mice had less severe kidney dysfunction, tubular damage, and apoptosis after cisplatin-induced AKI. Furthermore, conditional disruption of TAK1 in proximal tubular epithelial cells reduced caspase-3 activation, proinflammatory molecule expression, and JNK phosphorylation in the kidney in cisplatin-induced AKI. Taken together, cisplatin activates TAK1-JNK signaling pathway to promote tubular epithelial cell apoptosis and inflammation in cisplatin-induced AKI. Targeting TAK1 could be a novel therapeutic strategy against cisplatin-induced AKI.
Keyphrases
- acute kidney injury
- wild type
- cardiac surgery
- signaling pathway
- oxidative stress
- transforming growth factor
- cell death
- induced apoptosis
- epithelial mesenchymal transition
- endoplasmic reticulum stress
- high fat diet induced
- cell proliferation
- high glucose
- early onset
- cancer therapy
- skeletal muscle
- tyrosine kinase
- adipose tissue
- cell cycle arrest
- smoking cessation
- long non coding rna
- replacement therapy