title: Renin induces apoptosis in podocytes through a receptor-mediated, angiotensin II-independent mechanism.
abstract: BACKGROUND
  Podocytes play an important role in the pathogenesis and progression of glomerulosclerosis. Various elements of the renin-angiotensin-aldosterone system can induce podocyte apoptosis. However, little is known about the direct effects of renin on podocytes.
  
  
  METHODS
  The authors used the mouse podocyte cell line to investigate the apoptotic effects mediated by the renin receptor. The authors used fluorescent staining and reverse-transcriptase polymerase chain reaction to detect renin receptor expression. Podocytes were incubated with renin for variable time periods. Apoptosis was evaluated by cell nucleus staining, and caspase-3, p38 and phospho-p38 mitogen-activated protein kinase (MAPK) were measured.
  
  
  RESULTS
  The authors found that both renin receptor mRNA and protein were expressed in the mouse podocyte cell line. Exposure of podocytes to renin induced podocyte apoptosis in a time- and dose-dependent manner, which was accompanied by upregulation of active caspase-3 and increased expression of p38 MAPK. p38 MAPK phosphorylation and apoptosis were inhibited when the cells were pretreated with p38 MAPK inhibitor. Transfection of renin receptor small interfering RNA attenuated the above changes induced by renin. Furthermore, the effects of renin were not altered by inhibition of angiotensin II-mediated effects using enalaprilat or losartan.
  
  
  CONCLUSIONS
  The authors conclude that the effects of renin are mediated through the activation of rennin receptor and are independent of angiotensin II generation.
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yuan
authors.forename: Zhi-Long
authors.initials: ZL
authors.lastname: Ren
authors.forename: Feng-Qi
authors.initials: FQ
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Ding
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D015870:Gene Expression; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D020935:MAP Kinase Signaling System; D051379:Mice; D050199:Podocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000494:pharmacology / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D048051:p38 Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D012083:Renin; D000093342:Prorenin Receptor