Mechanism of Proliferation of Cultured Human Corneal Endothelial Cells

Abstract

Because human corneal endothelial cells (HCECs) do not proliferate once the endothelial monolayer has formed, corneal wound healing is believed to be mediated by cell enlargement or migration, rather than by proliferation. However, the cellular mechanisms involved in wound healing by HCECs have not been fully determined. In this review, we focus on the effects of promyelocytic leukemia zinc finger (PLZF), a DNA-binding transcription factor, and transforming growth factor (TGF)-β2 on the proliferation and migration of cultured HCECs. Involvement of the mitogen-activated protein kinase (MAPK) signaling pathway in the migration of HCECs was also investigated. Expression of PLZF mRNA decreased as cell-cell contact was disrupted and returned to the original level as cell-cell contact was re-formed. Assessment with a real-time cell electronic sensing system revealed that proliferation of cultured HCECs was inhibited after infection with Ad-PLZF and exposure to TGF-β2. Migration of cultured HCECs was increased by TGF-β2 through p38 MAPK activation. We conclude that PLZF expression in cultured HCECs is closely related to the formation of cell-cell contact and that TGF-β2 suppresses proliferation of cultured HCECs, while promoting their migration through p38 MAPK activation.

PTEN Inhibition Accelerates Corneal Endothelial Wound Healing through Increased Endothelial Cell Division and Migration

“…TGF-β2 has been reported to promote CEC migration by activating the P38 MAPK and PI3Ks signaling pathways. 28,29 In our study, enhanced migration of CECs was observed in response to TGF-β2, which could be completely blocked by LY294002, an inhibitor of PI3K/Akt (Fig 4). Meanwhile, inhibition of PTEN by bpV(pic) also accelerated CEC migration.…”

“…It is known that TGF-β2 promotes CEC migration through activation of P38 mitogen-activated protein kinases (MAPK) and PI3Ks signaling pathways. 28,29 Previous reports have demonstrated that downregulation of PTEN at the corneal epithelial wound edges facilitated the migration of peripheral corneal epithelial cells by increased Akt activation to significantly enhance the wound healing rate of corneal epithelial injury. 20,30 Considering the enhanced effect on cell migration, we aimed to explore if PTEN inhibition acted to synergize with the effects with TGF-β2 on CEC migration.…”

Corneal injury: Clinical and molecular aspects

“…The discovery of corneal endothelial stem cells could be highly beneficial in treating injured/lost endothelial cells. A review by Joko et al 2017 concluded that promyelocytic leukemia zinc finger (PLZF) expression in cultured CECs was closely related to the formation of cell-cell contact. Additionally, TGFβ2 suppressed proliferation of cultured human CECs while promoting their migration through p38 MAPK activation (Joko et al 2017).…”

“…A review by Joko et al 2017 concluded that promyelocytic leukemia zinc finger (PLZF) expression in cultured CECs was closely related to the formation of cell-cell contact. Additionally, TGFβ2 suppressed proliferation of cultured human CECs while promoting their migration through p38 MAPK activation (Joko et al 2017). Rho-associated protein kinase (ROCK) pathway, a signal cascade involved in sensing cell tension, has been implicated in endothelial migration, adhesion, and proliferation.…”

Identificação de um novo motivo peptídico específico para a vasculatura cerebral e que diferencia as barreiras hematoenfálica e hematoretiniana

“…A heterogeneidade vascular tem sido demonstrada em diversos tecidos e órgãos, utilizando uma ampla variedade de ensaios PASQUALINI & RUOSLAHTI, 1996;;RAJOTTE et al, 1998). Imagens obtidas por microscopia eletrônica de transmissão forneceram umas das primeiras descrições de diversidade fenotípica entre células endoteliais da microcirculação pulmonária de ratos (DEFOUW, 1988); ensaios de imunohistoquímica e hibridização in situ são utilizados para mapear a expressão de proteínas ou RNA mensageiro em leitos vasculares específicos (Joko et al, 2017;Guo et al, 2014) ; análises de microarray são utilizados para mapear a expressão gênica específica de diferentes populações de células endoteliais (HUANG et al, 2018); utilizando bibliotecas de phage display de peptídeos in vivo, é possível selecionar peptídeos com migração específica para diferentes leitos vasculares (ARAP et al, 2002;PASQUALINI & RUOSLAHTI, 1996;RAJOTTE et al, 1998).…”