Inhibition of α-Smooth Muscle Actin Expression and Migration of Pterygium Fibroblasts by Coculture with Amniotic Mesenchymal Stem Cells

Sha, Xianyi; Wen, Yan; Liu, Zhiping; Li, Song; Peng, Juan; Xie, Lifei

doi:10.3109/02713683.2014.900806

Cited by 8 publications

(5 citation statements)

References 34 publications

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“…Since smooth muscle cells seemed to be the most significantly enriched cell type in pterygia, the expression of known markers of smooth muscle cells as well as of myofibroblasts (34,35) was analyzed, the latter being not included within the xCell algorithm (Figure 2B). The results indicated that myofibroblasts represent the most differentially enriched cell type in pterygium specimens, which supports their assumed role in the pathogenesis of the disease (2,35,(40)(41)(42). Current evidence suggests that myofibroblasts emerge from conjunctival epithelial cells through the process of epithelial-mesenchymal transition (3,35).…”

Section: Discussionsupporting

confidence: 52%

Characterization of the Cellular Microenvironment and Novel Specific Biomarkers in Pterygia Using RNA Sequencing

et al. 2022

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With a worldwide prevalence of ~12%, pterygium is a common degenerative and environmentally triggered ocular surface disorder characterized by wing-shaped growth of conjunctival tissue onto the cornea that can lead to blindness if left untreated. This study characterizes the transcriptional profile and the cellular microenvironment of conjunctival pterygia and identifies novel pterygia-specific biomarkers. Formalin-fixed and paraffin-embedded pterygia as well as healthy conjunctival specimens were analyzed using MACE RNA sequencing (n = 8 each) and immunohistochemistry (pterygia n = 7, control n = 3). According to the bioinformatic cell type enrichment analysis using xCell, the cellular microenvironment of pterygia was characterized by an enrichment of myofibroblasts, T-lymphocytes and various antigen-presenting cells, including dendritic cells and macrophages. Differentially expressed genes that were increased in pterygia compared to control tissue were mainly involved in autophagy (including DCN, TMBIM6), cellular response to stress (including TPT1, DDX5) as well as fibroblast proliferation and epithelial to mesenchymal transition (including CTNNB1, TGFBR1, and FN1). Immunohistochemical analysis confirmed a significantly increased FN1 stromal immunoreactivity in pterygia when compared to control tissue. In addition, a variety of factors involved in apoptosis were significantly downregulated in pterygia, including LCN2, CTSD, and NISCH. Furthermore, 450 pterygia-specific biomarkers were identified by including transcriptional data of different ocular surface pathologies serving as controls (training group), which were then validated using transcriptional data of cultured human pterygium cells. Among the most pterygia-specific factors were transcripts such as AHNAK, RTN4, TPT1, FSTL1, and SPARC. Immunohistochemical validation of SPARC revealed a significantly increased stromal immunoreactivity in pterygia when compared to controls, most notably in vessels and intravascular vessel wall-adherent mononuclear cells. Taken together, the present study provides new insights into the cellular microenvironment and the transcriptional profile of pterygia, identifies new and specific biomarkers and in addition to fibrosis-related genes, uncovers autophagy, stress response and apoptosis modulation as pterygium-associated processes. These findings expand our understanding of the pathophysiology of pterygia, provide new diagnostic tools, and may enable new targeted therapeutic options for this common and sight-threatening ocular surface disease.

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Section: Discussionsupporting

confidence: 52%

Characterization of the Cellular Microenvironment and Novel Specific Biomarkers in Pterygia Using RNA Sequencing

et al. 2022

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“…Moreover, researches also indicate that ACTA2 potentiates metastatic potential of human lung cancer cells via enhancing actin filament assembling [12,13]. In addition, investigations delineate that ACTA2 could improve the migration potential of fibroblasts and mesenchymal stem cells [14][15][16]. Whether ACTA2 expresses in NSCs and its role in NSC migration still remain unexplored.…”

Section: Introductionmentioning

confidence: 99%

Actin Alpha 2 (ACTA2) Downregulation Inhibits Neural Stem Cell Migration through Rho GTPase Activation

Zhang

Jiang

Zhang

et al. 2020

Stem Cells International

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Although neural stem cells (NSCs) could migrate towards lesions after central nervous system (CNS) injury, the migration ability always is restricted due to the disturbed composition and density of the adhesion ligands and extracellular matrix (ECM) gradient after CNS injury. To date, various methods have been developed to enhance NSC migration and a number of factors, which are affecting NSC migration potential, have been identified. Here, primary NSCs were cultured and the expression of actin alpha 2 (ACTA2) in NSCs was determined using reverse transcription polymerase chain reaction (RT-PCR) and immunostaining. Next, the role of ACTA2 in regulating NSC migration and the potential mechanism was explored. Our results demonstrated that ACTA2 expressed in NSCs. Meanwhile, downregulated ACTA2 using siRNA inhibited NSC migration through hindering actin filament polymerization via increasing RhoA expression and decreasing Rac1 expression. The present study might enrich the basic knowledge of ACTA2 in NSC migration and open an avenue for enhancing NSC migration potential, subsequently providing an intervention target for functional recovery after CNS injury.

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“…Coculture of human amniotic mesenchymal stem cells (hAMSCs) with pterygium fibroblasts also showed the anti‐EMT effect by inhibition of α‐smooth muscle actin. Also, proximity with hAMSCs led to a diminution in the migratory phenotype of pterygial fibroblasts (Sha et al, ). These findings elucidated how hAMSCs are preventing the development of pterygium through abrogating TGFβ and the Notch signaling pathways.…”

Section: Discussion and Literature Reviewmentioning

confidence: 99%

“…The normal arrows show the role of signaling in pterygium which have been indicated in previous works, but the dotted arrows show the signaling roles which only confirmed in cancer cells and it is suggested to investigate in pterygium cases. APC: antigen-presenting cell; EGFR: epidermal growth factor receptor; EMT: epithelial−mesenchymal transition; miR: microRNA; MMP: metalloproteinase; mTOR: mammalian target of rapamycin; NF-κB: nuclear factor-κB; PI3K: phosphoinositide 3-kinase; PTEN: phosphatase and tensin homolog; TCF4: transcription factor 4; TGFβ: transforming growth factor β; TNF-α: tumor necrosis factoruPA, urokinase-type plasminogen activator; Zeb1: zinc finger E-box binding homeobox 1 [Color figure can be viewed at wileyonlinelibrary.com] phenotype of pterygial fibroblasts(Sha et al, 2014). These findings elucidated how hAMSCs are preventing the development of pterygium through abrogating TGFβ and the Notch signaling pathways.Pirfenidone, which is known as a potential antifibrotic drug, has shown inhibitory effects on proliferation and migration on pterygium fibroblasts through diminishing expression of TGFβ at the protein level in a dose-dependent manner.…”

mentioning

confidence: 99%

Signaling roadmap to epithelial–mesenchymal transition in pterygium, TWIST1 centralized

Meshkani

Kooshan

Moghadam

et al. 2019

Journal Cellular Physiology

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Pterygium as a complex disease shares common features with other malignant cells in its onset recurrence and especially epithelial–mesenchymal transition (EMT) transition. Although using different approaches including conjunctival autografts, amniotic membrane, radiotherapy, mitomycin C (MMC) has shown promising insights in the inhibition of pterygium recurrence, it needs to be investigated in more details in molecular pathways to present adjuvant target therapy. In this study, we aimed to evaluate the expression of and then illustrate the role of signaling pathways on EMT in pterygium. Using real‐time polymerase chain reaction, the twist‐related protein 1 (TWIST1) expression was compared in primary pterygium and normal conjunctiva. This study assessed the mRNA expression, as well as the association between the clinicopathological indices and the gene expression level. The expression level of TWIST1 was overexpressed in 36% of our cohort ( n = 76). There was a significant positive correlation between recurrence with grade T, grade V and a significant negative correlation with growth activity. Our vast literature review on different signaling pathways in pterygium showed that EMT has centralization role in recurrence of this disease. Our data confirmed that EMT is important in the recurrence of pterygium samples and different signaling pathways end up activating the EMT markers. It is suggested to evaluate the environmental factors and their correlation with molecular markers to select favorable treatment for this kind of diseases.

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Inhibition of α-Smooth Muscle Actin Expression and Migration of Pterygium Fibroblasts by Coculture with Amniotic Mesenchymal Stem Cells

Abstract: These results suggested that hAMSCs have the potential to inhibit the generation and invasiveness of pterygium in vitro.

Cited by 8 publications

References 34 publications

Characterization of the Cellular Microenvironment and Novel Specific Biomarkers in Pterygia Using RNA Sequencing

Characterization of the Cellular Microenvironment and Novel Specific Biomarkers in Pterygia Using RNA Sequencing

Actin Alpha 2 (ACTA2) Downregulation Inhibits Neural Stem Cell Migration through Rho GTPase Activation

Signaling roadmap to epithelial–mesenchymal transition in pterygium, TWIST1 centralized

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