title: Mycophenolate mofetil and valsartan inhibit podocyte apoptosis in streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  To investigate the effects of mycophenolate mofetil on apoptosis and the expression of Bax and Bcl-2 of podocytes in rats with diabetic nephropathy.
  
  
  METHODS
  A total of 40 male rats were randomly divided into two groups: healthy control group (NC, n = 8) and diabetic nephropathy group (DN, n = 32). The diabetic rat models were induced by streptozotocin, which was injected intraperitoneally. After the DN model was established successfully, the DN group was subdivided into four groups: (1) group treated with the dissolvent (DN), (2) group treated with mycophenolate mofetil (DN + M), (3) group treated with valsartan (DN + V) and (4) group treated with mycophenolate mofetil and valsartan (DN + MV). After 16 weeks of treatment, kidney and body weight, urinary protein level and serum glucose were measured. Histomorphology of renal tissue was observed by an optical microscope. Apoptosis of podocytes was determined by transferase-mediated dUTP nick-end labeling (TUNEL) test. The expression of nephrin and Wilms' tumor suppressor gene (WT1) were detected by immunohistochemistry and real-time PCR, and the protein expression of Bax and Bcl-2 were examined by Western blot.
  
  
  RESULTS
  The mRNA and protein expression of nephrin and WT1 were both downregulated. The apoptosis rate, the expression of Bax, caspase-3 activity and cleavage increased, while the expression of Bcl-2 decreased in the DN group compared with the NC group. However, they were all improved in the groups treated with either mycophenolate mofetil or valsartan.
  
  
  CONCLUSIONS
  Mycophenolate mofetil can protect renal function by increasing Bcl-2 expression and decreasing Bax expression and podocyte apoptosis rate, thereby reducing proteinuria.
authors.affiliation: Department of Nephrology, the Second Hospital of Shandong University, Jinan, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guangju
authors.initials: G
authors.lastname: Guan
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Qi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000008:administration & dosage*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan; D025721:WT1 Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D008565:Membrane Proteins; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D013777:Tetrazoles; D025721:WT1 Proteins; D051028:bcl-2-Associated X Protein; C113267:nephrin; D000068756:Valsartan; D053148:Caspase 3; D014633:Valine; D009173:Mycophenolic Acid