Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00142)
Name |
Unilateral ureteral obstruction
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ICD |
ICD-11: MG30
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Full List of Target(s) of This Ferroptosis-centered Disease
NADPH oxidase 4 (NOX4)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Unilateral ureteral obstruction [ICD-11: MG30] | ||||
Responsed Drug | Tectorigenin | Investigative | |||
Responsed Regulator | Mothers against decapentaplegic homolog 3 (SMAD3) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | mRTECs (Mouse renal tubular epithelial cells) | ||||
In Vivo Model |
The male C57BL/6 mice (8 weeks old, 22-25 g body weight) used in this study were purchased from Dashuo Bio-Technique Co. Ltd. (Chengdu, China) and were maintained in 12 hr of light/12 hr of darkness. The mice were randomly divided into the following 4 groups (n = 8 per group): Sham, UUO, UUO with tectorigenin (20 mg/kg/day, dissolved in saline with 10% dimethyl sulfoxide [DMSO]) or irbesartan (IRB, a positive control, 20 mg/kg/day) treatment. After anesthesia with 1% pentobarbital, the left ureter was exposed through the lower left incision on the midline of the back and blocked by two-point ligation with 40 silk thread as previously described. The Sham-operated mice underwent the same operation but absence of ligation. The tectorigenin and IRB group were administered intraperitoneally with drug daily for 7 consecutive days since surgery. Sham-operated mice and UUO mice were received the equal volume of solvent.
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Response regulation | Tectorigenin exerts as a Smad3 inhibitor to suppress Smad3 activation through an Nox4-dependent mechanism. Tectorigenin protects against unilateral ureteral obstruction by inhibiting Smad3-mediated ferroptosis and fibrosis. | ||||