title: Protein tyrosine phosphatase 1B regulates the activity of retinal pigment epithelial cells.
abstract: OBJECTIVE
  To determine whether protein tyrosine phosphatase 1B (PTP1B) is expressed in rat retinal pigment epithelium (RPE) cells, to evaluate whether inhibition of PTP1B contributes to initiation of RPE cells into an active state, and to investigate the signaling pathways involved in this process.
  
  
  METHODS
  Rat retinas were detached by trans-scleral injection of 1.4% sodium hyaluronate into the subretinal space. Immunocytochemistry evaluated the expression of PTP1B in RPE cells located at normal and detached retinas. From the cultured RPE cells treated with TCS-401, cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetracolium bromide assay, and the protein expression levels of cyclin A and cyclin D1 were determined. The effect of TCS-401 on cell differentiation was confirmed by immunostaining for α-smooth muscle actin and by western blot. Cell migration activity and PTP1B signaling mechanism were determined. Migration Assay was used to evaluate cell migration activity. PTP1B signaling mechanism was determined by use of PD98059 and LY294002.
  
  
  RESULTS
  PTP1B was expressed in the RPE layer of the normal retina. After retinal detachment, weak immunolabeling of PTP1B was seen in the RPE cells. TCS-401 promoted the proliferation and expression of cyclin A and cyclin D1 in RPE cells. TCS-401 induced RPE cells to differentiate toward better contractility and motility. A migration assay proved that inhibiting PTP1B improved the migratory activity of RPE cells. TCS-401 activated extracellular signal-regulated kinase (Erk) and protein kinase B (Akt) phosphorylation. Pretreatment with PD98059 and LY294002 abolished TCS-401-induced activation of Erk, Akt, cell proliferation, and cell migration.
  
  
  CONCLUSIONS
  PTP1B may be involved in regulating the active state of RPE cells. The inhibition of PTP1B promoted the proliferation, myofibroblast differentiation, and migration of RPE cells, and MEK/Erk and PI3K/Akt signaling pathways played important roles in the proliferation and migration process.
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Zhao-dong
authors.initials: ZD
authors.lastname: Du
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Li-ting
authors.initials: LT
authors.lastname: Hu
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Gui-qiu
authors.initials: GQ
authors.lastname: Zhao
authors.affiliation: Peking University Eye Center, Peking University Third Hospital, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Peking University Eye Center, Peking University Third Hospital, Beijing, China.
authors.forename: Zhi-zhong
authors.initials: ZZ
authors.lastname: Ma
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012163:Retinal Detachment / Q000201:enzymology / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one