title: Indoxyl sulfate induces renin release and apoptosis of kidney mesangial cells.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Biomedical Engineering, Chung Yuan Christian University.
authors: Wei-Jie
authors: WJ
authors: Wang
authors: Mei-Hua
authors: MH
authors: Cheng
authors: Mao-Feng
authors: MF
authors: Sun
authors: Sheng-Feng
authors: SF
authors: Hsu
authors: Ching-Sung
authors: CS
authors: Weng
mesh_terms: D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007200:Indican / Q000633:toxicity*; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000809:Angiotensins; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; D053148:Caspase 3; D012083:Renin; D007200:Indican