Indoxyl sulfate induces apoptosis and activates the renin-angiotensin system in rat renal mesangial cells, providing mechanistic insight into its pathological role in chronic kidney disease.
Indoxyl sulfate effects in rat mesangial cells should not change CKD practice; leaves open human relevance pending in vivo validation.
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.
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Wang et al. (2014) studied this question.
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