Pigment epithelium‐derived factor peptide promotes limbal stem cell proliferation through hedgehog pathway

Fan, Nai Wen; Ho, Tsung Chuan; Wu, Cheng Wen; Tsao, Yeou‐Ping

doi:10.1111/jcmm.14364

Cited by 14 publications

(15 citation statements)

References 42 publications

(113 reference statements)

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“… 1 Cyclin D1 is a well-known cell cycle regulator and a transcriptional target of the Hippo-Yap signaling pathway, 47 which is also a key factor in regulating limbal stem cell proliferation. 48 Our study proved Agrin could inhibit the phosphorylation of Yap1 and modulate the expression of downstream Cyclin D1, which further activating limbal stem cell proliferation.…”

Section: Discussionmentioning

confidence: 58%

Agrin Promotes Limbal Stem Cell Proliferation and Corneal Wound Healing Through Hippo-Yap Signaling Pathway

Hou

Liu

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Purpose To investigate the effect and mechanism of Agrin on limbal stem cell proliferation and corneal wound healing. Methods Limbal stem cells were isolated and treated with different concentrations of Agrin. CCK-8 and cell proliferation markers (Ki67 and pH3) were detected to evaluate cell numbers or proliferative potential of limbal stem cells. The corneal epithelium wound model was induced by debridement of central corneal epithelial, and the effects of Agrin on limbal stem cell proliferation and corneal epithelial wound healing rate were determined. Results Agrin promoted the proliferation of cultured limbal stem cells in vitro and increased the expression level of p63α rather than keratin 12. Furthermore, Agrin accelerated the wound healing rate of corneal epithelium through activating limbal stem cell proliferation in vivo. In terms of mechanism, Agrin could facilitate the dephosphorylation of Yap1, which contributed to the nuclear translocation of Yap1 and expression of Cyclin D1, and subsequently promoted proliferation of limbal stem cells. Conclusions Agrin promotes the proliferation of limbal stem cells and accelerates the healing rate of corneal wound through Hippo-Yap signaling pathway.

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Section: Discussionmentioning

confidence: 58%

Agrin Promotes Limbal Stem Cell Proliferation and Corneal Wound Healing Through Hippo-Yap Signaling Pathway

Hou

Liu

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…Growth factors are key components for the development and function of the limbal niche and accumulating evidence suggested that they play important roles in regulating LESCs survival and development 22,38,41‐46 . In addition, as shown above, LNCs act in a paracrine fashion to support LESCs in vitro, and so, we decided to analyse whether SOX10 acts through growth factors to influence the survival of LESCs in LNCs.…”

Section: Resultsmentioning

confidence: 99%

“…that they play important roles in regulating LESCs survival and development. 22,38,[41][42][43][44][45][46] In addition, as shown above, LNCs act in a paracrine fashion to support LESCs in vitro, and so, we decided to analyse whether SOX10 acts through growth factors to influence the survival of LESCs in LNCs. To identify which factors might be involved, we compared the expression of a series of growth factor genes in si-Sox10 transfected LNCs vs si-C or mock-transfected LNCs.…”

Section: Sox10 Controls the Ability Of Lncs To Serve As A Niche Formentioning

confidence: 99%

KIT ligand produced by limbal niche cells under control of SOX10 maintains limbal epithelial stem cell survival by activating the KIT/AKT signalling pathway

Wang

Lai

et al. 2020

J Cellular Molecular Medi

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Limbal epithelial stem cells (LESCs) play critical roles in regulating homeostasis of the corneal epithelium. Loss of LESCs leads to severe corneal disease, called limbal epithelial stem cell deficiency (LSCD), which is associated with corneal neovascularization, stromal scarring and impaired visual acuity. 1 LESCs transplantation represents a feasible therapeutic approach to LSCD, but according to statistical analysis of clinical trials, this approach has nevertheless failed to improve vision in 26.7%-60% of LSCD patients. These therapeutic failures may be due to the limited life span of LESCs. 2-12 Evidently, a detailed analysis of the molecular mechanisms of LESC maintenance is of paramount importance to design approaches to enhance the success of therapeutic transplantation, or better still, to be able to interfere with LESC loss early in the disease process. 13 The maintenance of adult stem cells relies on stem cell niches whose microenvironment contains an extracellular matrix and cells that provide autocrine and paracrine signals necessary for the proper function of the respective stem cells. There is increasing evidence that one of the major type of niche cells supporting

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“…In addition, integrated RNA-seq and proteomic pathway analyses revealed changes in Hedgehog signaling and TGF-β ( Figure 3 C). Study of Hedgehog in mice indicates that it may play a role in both corneal epithelial regeneration and limbal epithelial maintenance [ 49 , 50 , 51 ]. TGF-β regulates several essential cellular processes in the cornea, such as local inflammatory responses and wound healing in ocular surface epithelial cells [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated Transcriptome and Proteome Analyses Reveal the Regulatory Role of miR-146a in Human Limbal Epithelium via Notch Signaling

Poe

Kulkarni

Leszczynska

et al. 2020

Cells

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MiR-146a is upregulated in the stem cell-enriched limbal region vs. central human cornea and can mediate corneal epithelial wound healing. The aim of this study was to identify miR-146a targets in human primary limbal epithelial cells (LECs) using genomic and proteomic analyses. RNA-seq combined with quantitative proteomics based on multiplexed isobaric tandem mass tag labeling was performed in LECs transfected with miR-146a mimic vs. mimic control. Western blot and immunostaining were used to confirm the expression of some targeted genes/proteins. A total of 251 differentially expressed mRNAs and 163 proteins were identified. We found that miR-146a regulates the expression of multiple genes in different pathways, such as the Notch system. In LECs and organ-cultured corneas, miR-146a increased Notch-1 expression possibly by downregulating its inhibitor Numb, but decreased Notch-2. Integrated transcriptome and proteome analyses revealed the regulatory role of miR-146a in several other processes, including anchoring junctions, TNF-α, Hedgehog signaling, adherens junctions, TGF-β, mTORC2, and epidermal growth factor receptor (EGFR) signaling, which mediate wound healing, inflammation, and stem cell maintenance and differentiation. Our results provide insights into the regulatory network of miR-146a and its role in fine-tuning of Notch-1 and Notch-2 expressions in limbal epithelium, which could be a balancing factor in stem cell maintenance and differentiation.

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Pigment epithelium‐derived factor peptide promotes limbal stem cell proliferation through hedgehog pathway

Cited by 14 publications

References 42 publications

Agrin Promotes Limbal Stem Cell Proliferation and Corneal Wound Healing Through Hippo-Yap Signaling Pathway

Agrin Promotes Limbal Stem Cell Proliferation and Corneal Wound Healing Through Hippo-Yap Signaling Pathway

KIT ligand produced by limbal niche cells under control of SOX10 maintains limbal epithelial stem cell survival by activating the KIT/AKT signalling pathway

Integrated Transcriptome and Proteome Analyses Reveal the Regulatory Role of miR-146a in Human Limbal Epithelium via Notch Signaling

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