|Protein tyrosine phosphatase 1B regulates the activity of retinal pigment epithelial cells|
|Du, Zhao-dong1; Hu, Li-ting1; Zhao, Gui-qiu1; Li, Ying2; Ma, Zhi-zhong2|
|WOS标题词||Science & Technology|
|类目[WOS]||Biochemistry & Molecular Biology ; Ophthalmology|
|研究领域[WOS]||Biochemistry & Molecular Biology ; Ophthalmology|
|关键词[WOS]||CORNEAL ENDOTHELIAL-CELLS ; GROWTH-FACTOR RECEPTOR ; MESENCHYMAL TRANSITION ; PROLIFERATIVE VITREORETINOPATHY ; SIGNALING PATHWAYS ; N-CADHERIN ; EXPRESSION ; PTP1B ; PROGRESSION ; INHIBITION|
Purpose: 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 alpha-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.
|项目编号||ZR2012HQ004 ; 1314180jch ; 2014174 ; QDFY134|
|资助机构||Shandong Natural Science Foundation ; Research Fund for Fundamental Research Project of Qingdao ; Scientific Research Fund of Huangdao District of Qingdao City ; Young People Scientific Research Fund of Affiliated Hospital, Qingdao University|
|作者单位||1.Peking Univ, Hosp 3, Ctr Eye, Beijing 100871, Peoples R China|
2.Qingdao Univ, Affiliated Hosp, Dept Ophthalmol, Qingdao 266003, Shandong, Peoples R China
|Du, Zhao-dong,Hu, Li-ting,Zhao, Gui-qiu,et al. Protein tyrosine phosphatase 1B regulates the activity of retinal pigment epithelial cells[J]. MOLECULAR VISION,2015,21:523-531.|
|APA||Du, Zhao-dong,Hu, Li-ting,Zhao, Gui-qiu,Li, Ying,&Ma, Zhi-zhong.(2015).Protein tyrosine phosphatase 1B regulates the activity of retinal pigment epithelial cells.MOLECULAR VISION,21,523-531.|
|MLA||Du, Zhao-dong,et al."Protein tyrosine phosphatase 1B regulates the activity of retinal pigment epithelial cells".MOLECULAR VISION 21(2015):523-531.|