title: Expression of mitogen-activated protein kinases in human renal dysplasia.
abstract: BACKGROUND
  We previously reported that the expression of mitogen-activated protein kinases (MAPKs) is developmentally regulated. Dysregulation of MAPKs may lead to kidney malformation. Thus, we investigated the expression of MAPKs in human renal dysplasia, one of the most common kidney malformations.
  
  
  METHODS
  Prenatal (gestational ages 20 to 36 weeks, N = 6) and postnatal (2 years old, N = 1) dysplastic kidneys, and normal kidneys (gestational ages 19 to 34 weeks, N = 4) were examined. Immunohistochemical studies were performed using antibodies against extracellular signal-regulated kinase (ERK), p38 MAPK (p38), c-Jun N-terminal kinase (JNK), phospho-MAPKs (P-MAPKs), and proliferating cell nuclear antigen (PCNA). Apoptosis was detected by the TUNEL method.
  
  
  RESULTS
  In dysplastic kidneys, proliferation was prominent in dysplastic tubules and also found in cyst epithelia. TUNEL staining was detected in dysplastic tubules and cysts, and occasionally in undifferentiated cells. p38 and anti-phospho-p38 (P-p38) were strongly expressed in dysplastic epithelia, but not detected in normal kidneys at any stage examined. On the other hand, JNK and P-JNK were positive in tubular epithelia of normal kidneys, whereas their expression was barely detectable in dysplastic tubules and cysts. ERK was expressed in all tubular segments, and P-ERK was detected in distal tubules and collecting ducts of normal kidneys. Dysplastic kidney epithelia stained exclusively positive for ERK and P-ERK.
  
  
  CONCLUSIONS
  p38 is ectopically expressed, and JNK is down-regulated in dysplastic kidney epithelia. Furthermore, dysplastic epithelia are exclusively positive for ERK and P-ERK. Activated p38 and ERK may mediate hyperproliferation of dysplastic tubules resulting in cyst formation, whereas down-regulated JNK expression may be the cause or the result of an undifferentiated state of dysplastic epithelia.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Sayu
authors.initials: S
authors.lastname: Omori
authors.forename: Ryuji
authors.initials: R
authors.lastname: Fukuzawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Hida
authors.forename: Midori
authors.initials: M
authors.lastname: Awazu
mesh_terms: D017209:Apoptosis; D018797:Cell Cycle Proteins; D002675:Child, Preschool; D054638:Dual Specificity Phosphatase 1; D004622:Embryo, Mammalian / Q000378:metabolism; D005333:Fetus; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases; D007668:Kidney / Q000002:abnormalities* / Q000196:embryology / Q000201:enzymology* / Q000503:physiopathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D018809:Proliferating Cell Nuclear Antigen; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases