title: Possible effect of lysophosphatidic acid on cell proliferation and involvement of lysophosphatidic acid and lysophosphatidic acid receptors in mechanical stretch-induced mitogen-activated protein kinase.
abstract: OBJECTIVE
  To determine whether lysophosphatidic acid activates the mitogen-activated protein kinase and increases DNA synthesis in human bladder smooth muscle cells, and to examine the involvement of lysophosphatidic acid and lysophosphatidic acid receptor in mechanical stretch-induced mitogen-activated protein kinase activation in cultured human bladder smooth muscle cells.
  
  
  METHODS
  TaqMan reverse transcription polymerase chain reaction was used to determine the mRNA expression levels of six lysophosphatidic acid receptor subtypes. Mitogen-activated protein kinase activity enhanced by either lysophosphatidic acid or mechanical stretch was measured by western blotting. The effect of lysophosphatidic acid on DNA synthesis was assessed by 5-bromo-2'-deoxy-uridine incorporation assay.
  
  
  RESULTS
  Lysophosphatidic acid 1 subtype mRNA was predominantly expressed (96%). Lysophosphatidic acid activated the mitogen-activated protein kinase in a concentration-dependent manner. C-jun NH2 -terminal kinase showed the highest activity among the three subsets of the mitogen-activated protein kinase family members (c-jun NH2 -terminal kinase, extracellular signal-regulated kinases, p38). Lysophosphatidic acid also increased incorporation of 5-bromo-2'-deoxy-uridine. These responses were suppressed by Ki16425 (lysophosphatidic acid receptor antagonist). Mechanical stretch mainly induced c-jun NH2 -terminal kinase activation. This activation was partially inhibited by Ki16425.
  
  
  CONCLUSIONS
  Lysophosphatidic acid might activate the c-jun NH2 -terminal kinase component of the mitogen-activated protein kinase family and DNA synthesis through lysophosphatidic acid receptors (presumably, through lysophosphatidic acid 1) in human bladder smooth muscle cells. The present study also implicates the involvement of lysophosphatidic acid and lysophosphatidic acid receptors in mechanical stretch-induced c-jun NH2 -terminal kinase activation. Lysophosphatidic acid receptor can be partially activated by mechanical stretching through lysophosphatidic acid-dependent or independent mechanism.
authors.affiliation: Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawashima
authors.affiliation: Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kushida
authors.affiliation: Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Shuko
authors.initials: S
authors.lastname: Kokubun
authors.affiliation: Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Homare
authors.initials: H
authors.lastname: Shiomi
authors.affiliation: Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Aikawa
authors.affiliation: Division of Bioengineering and LUTD Research, Nihon University College of Engineering, Koriyama, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ikegami
authors.affiliation: Division of Bioengineering and LUTD Research, Nihon University College of Engineering, Koriyama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomiya
authors.affiliation: Division of Bioengineering and LUTD Research, Nihon University College of Engineering, Koriyama, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008246:Lysophospholipids / Q000737:chemistry*; D020935:MAP Kinase Signaling System; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D001743:Urinary Bladder / Q000166:cytology
chemical_list: D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C032881:lysophosphatidic acid
keywords: bladder hyperplasia; bladder outlet obstruction; c-jun NH2-terminal kinase; lysophosphatidic acid; mechanical stress