Indoxyl sulfate induces renin release and apoptosis of kidney mesangial cells

Background: Indoxyl sulfate is considered to play a pathological role in the progression of chronic kidney disease. The aim of this study was to investigate the deleterious effects of indoxyl sulfate on kidney mesangial cells. Materials and Methods: Rat renal mesangial cells were exposed to indoxyl...

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Published in:Journal of toxicological sciences 2014/08/01, Vol.39(4), pp.637-643
Main Authors: Wang, Wei-Jie, Cheng, Mei-Hua, Sun, Mao-Feng, Hsu, Sheng-Feng, Weng, Ching-Sung
Format: Article
Language:English
Subjects:
Angiotensins - metabolism
Animals
Apoptosis
Apoptosis - drug effects
Apoptosis - genetics
Caspase 3 - metabolism
Cell Survival - drug effects
Cells, Cultured
CKD
Dose-Response Relationship, Drug
Indican - toxicity
Indoxyl sulfate
Kidney mesangial cell
Mesangial Cells - drug effects
Mesangial Cells - metabolism
Mesangial Cells - pathology
Peptidyl-Dipeptidase A - genetics
Peptidyl-Dipeptidase A - metabolism
Rats
Renin - genetics
Renin - metabolism
Renin-Angiotensin System - drug effects
Renin-angiotension-system
RNA, Messenger - metabolism
Time Factors
Up-Regulation - drug effects
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Summary:Background: Indoxyl sulfate is considered to play a pathological role in the progression of chronic kidney disease. The aim of this study was to investigate the deleterious effects of indoxyl sulfate on kidney mesangial cells. Materials and Methods: Rat renal mesangial cells were exposed to indoxyl sulfate at a serial concentrations. Cytotoxicity of indoxyl sulfate on renal mesangial cells was determined using MTT assay. Protein levels of cleaved caspase-3, angiotensin, angiotensin converting enzyme (ACE) and renin were detected by immunoblotting. Reverse transcriptional PCR was performed to determine the mRNA expression. Results: Level of cleaved caspase-3 was augmented while the cell viability was inhibited by indoxyl sulfate in a dose-dependent manner. The mRNA expressions of pro-renin and ACE were upregulated in mesangial cells exposed to indoxyl sulfate. Level of renin and ACE was increased in response to indoxyl sulfate exposure in time-dependent fashion. Conclusion: Indoxyl sulfate increased viability and induced cell death of renal mesangial cells, which is time-dependent. The loss of cell viability is attributed to caspase-3 activity through apoptosis pathway. RAS in renal mesangial cells is activated in response to indoxyl sulfate treatment.
ISSN:0388-1350
1880-3989
DOI:10.2131/jts.39.637