Expression and Function of ZEB1 in the Cornea

Zhang, Yingnan; Liu, Xiao; Liang, Wei; Dean, Douglas C.; Zhang, Lijun; Liu, Yongqing

doi:10.3390/cells10040925

Cited by 15 publications

(9 citation statements)

References 59 publications

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“…ZEB1 is involved in cell differentiation and transformation in development and pathogenesis of many diseases including cancer and tissue fibrosis 7 . Mutations of ZEB1 have been linked to stem cell inefficiency 36 , immune deficiency 37 and corneal endothelial dystrophy 38,39 . In adult tissues, abnormal activation of ZEB1 often results in cancer metastasis 40 and scar formation 41 that lead to tissue malfunction.…”

Section: Discussionmentioning

confidence: 99%

Zeb1 facilitates corneal epithelial wound healing by maintaining corneal epithelial cell viability and mobility

et al. 2023

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The cornea is the outmost ocular tissue and plays an important role in protecting the eye from environmental insults. Corneal epithelial wounding provokes pain and fear and contributes to the most ocular trauma emergency assessments worldwide. ZEB1 is an essential transcription factor in development; but its roles in adult tissues are not clear. We identify Zeb1 is an intrinsic factor that facilitates corneal epithelial wound healing. In this study, we demonstrate that monoallelic deletion of Zeb1 significantly expedites corneal cell death and inhibits corneal epithelial EMT-related cell migration upon an epithelial debridement. We provide evidence that Zeb1-regulation of corneal epithelial wound healing is through the repression of genes required for Tnfa-induced epithelial cell death and the induction of genes beneficial for epithelial cell migration. We suggest utilizing TNF-α antagonists would reduce TNF/TNFR1-induced cell death in the corneal epithelium and inflammation in the corneal stroma to help corneal wound healing.

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Section: Discussionmentioning

confidence: 99%

Zeb1 facilitates corneal epithelial wound healing by maintaining corneal epithelial cell viability and mobility

et al. 2023

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“…Based on the current model, ZEB1 is activated by the transforming growth factor beta (TGFβ) through TGFβ-SMAD signaling pathway ( Sanchez-Tillo et al., 2012 ). Mutations of ZEB1 have been linked to stem cell inefficiency ( Wang et al., 2020 ), immune deficiency ( Dean et al., 2015 ), and corneal endothelial dystrophy ( Liu et al., 2008b ; Zhang et al., 2021 ). We and others find that ZEB1 promotes both cell proliferation by inhibiting cyclin-dependent kinase inhibitors (CDKI) ( Liu et al., 2008a ) and migration by enhancing EMT properties ( Chen et al., 2017 ; Xue et al., 2019 ), whereas the loss of ZEB1 function mutation leads to cell senescence ( Liu et al., 2008a ).…”

Section: Introductionmentioning

confidence: 99%

Zeb1 regulation of wound-healing-induced inflammation in alkali-damaged corneas

et al. 2022

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“…In this study, we screened out zinc finger E-box-binding homebox 1 (ZEB1) as a significantly downregulated gene in OP using Gene Expression Omnibus (GEO) microarray. ZEB1 is a major transcription factor responsible for epithelial to mesenchymal transition and regulates cell differentiation and transformation [ 6 ]. For instance, a recent study reported that ZEB1 stimulated odontoblast differentiation in the early stage by directly binding to and increasing the enhancer activity of Dspp [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

ZEB1 regulates bone metabolism in osteoporotic rats through inducing POLDIP2 transcription

2022

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Background Osteoporosis (OP) is a common metabolic bone disease mainly involving bone remodeling and blood vessels. The current study aimed to explore the role of zinc finger E-box binding homeobox 1 (ZEB1) in OP. Methods First, gene expression microarrays for OP were downloaded from the Gene Expression Omnibus database and analyzed to screen for potential targets. Subsequently, a rat OP model was constructed using ovariectomy (OVX), and osteoblastic and osteoclastic differentiation and alterations in osteoporotic symptoms were observed upon intraperitoneal injection of oe-ZEB1 lentiviral vectors. DNA polymerase delta interacting protein 2 (POLDIP2) was predicted to be a downstream target of ZEB1, which was validated by ChIP-qPCR and dual-luciferase experiments. RAW264.7 cells were subjected to lentiviral vector infection of oe-ZEB1 and/or sh-POLDIP2, followed by RANKL treatment to induce osteoclast differentiation. Results ZEB1 was poorly expressed in blood samples of postmenopausal patients with OP and in bone tissues of OVX-treated rats. Overexpression of ZEB1 or POLDIP2 in OVX rats promoted osteoblastogenesis and inhibited osteoclast differentiation. In RANKL-treated RAW264.7 cells, the transcription factor ZEB1 enhanced the expression of POLDIP2, and silencing of POLDIP2 attenuated the inhibitory effect of oe-ZEB1 on the differentiation of macrophages RAW264.7 to osteoclasts. Conclusions ZEB1 promotes osteoblastogenesis and represses osteoclast differentiation, ultimately reducing the occurrence of postmenopausal OP by elevating the expression of POLDIP2.

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Expression and Function of ZEB1 in the Cornea

Cited by 15 publications

References 59 publications

Zeb1 facilitates corneal epithelial wound healing by maintaining corneal epithelial cell viability and mobility

Zeb1 facilitates corneal epithelial wound healing by maintaining corneal epithelial cell viability and mobility

Zeb1 regulation of wound-healing-induced inflammation in alkali-damaged corneas

ZEB1 regulates bone metabolism in osteoporotic rats through inducing POLDIP2 transcription

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