Exosomes mediate an epithelial‐mesenchymal transition cascade in retinal pigment epithelial cells: Implications for proliferative vitreoretinopathy

Zhang, Yao; Wang, Kaizhe; Pan, Jiaping; Yang, Shuai; Yao, Haipei; Li, Min; Li, Hui; Lei, Hetian; Jin, Haiying; Wang, Fang

doi:10.1111/jcmm.15951

Cited by 29 publications

(28 citation statements)

References 63 publications

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“…Exosomes are nano-sized extracellular vesicles originating from the endosomal pathway that exist in almost all body fluids and are promising source of biomarkers 28 . Exosomes carry a cargo of proteins, lipids and nucleic acids, that can participate in cell-to-cell signaling affecting nearby and distant cells 29 , playing a role in EMT and peritoneal fibrosis 30 , 31 , and in angiogenesis processes 32 .…”

Section: Introductionmentioning

confidence: 99%

Proteomic profile of mesothelial exosomes isolated from peritoneal dialysis effluent of children with focal segmental glomerulosclerosis

Bruschi

Porta

Panfoli

et al. 2021

Sci Rep

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Peritoneal dialysis (PD) is the worldwide recognized preferred dialysis treatment for children affected by end-stage kidney disease (ESKD). However, due to the unphysiological composition of PD fluids, the peritoneal membrane (PM) of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by steroid resistant primary focal segmental glomerulosclerosis, a rare glomerular disease leading to nephrotic syndrome and ESKD, seem more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE) of 6 pediatric patients with focal segmental glomerular sclerosis (FSGS) versus 6 patients affected by other primary renal diseases (No FSGS). Our omic study demonstrated that, despite the high overlap in the protein milieu between the two study groups, machine learning allowed to identify a core list of 40 proteins, with ANXA13 as most promising potential biomarker, to distinguish, in our patient population, peritoneal dialysis effluent exosomes of FSGS from No FSGS patients (with 100% accuracy). Additionally, the Weight Gene Co-expression Network Analysis algorithm identified 17 proteins, with PTP4A1 as the most statistically significant biomarker associated to PD vintage and decreased PM function. Altogether, our data suggest that mesothelial cells of FSGS patients are more prone to activate a pro-fibrotic machinery. The role of the proposed biomarkers in the PM pathology deserves further investigation. Our results need further investigations in a larger population to corroborate these findings and investigate a possible increased risk of PM loss of function or development of encapsulating peritoneal sclerosis in FSGS patients, thus to eventually carry out changes in PD treatment and management or implement new solutions.

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Section: Introductionmentioning

confidence: 99%

Proteomic profile of mesothelial exosomes isolated from peritoneal dialysis effluent of children with focal segmental glomerulosclerosis

Bruschi

Porta

Panfoli

et al. 2021

Sci Rep

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“…Recent studies have evidenced that the existence of miRNA in the extracellular vesicles released by RPE cells may contribute to retinal pathophysiolgical processes [ 35 , 36 ]. To characterize the profiles of miR-100 biosynthesis and its release in response to oxidative stress, we first examined the cytotoxic effect of H 2 O 2 -mimicked oxidative stress in human ARPE-19 RPE cells by exposing cells to various concentrations of H 2 O 2 , and consequent cell viability was determined by MTT cytotoxicity assay.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-100 Mediates Hydrogen Peroxide-Induced Apoptosis of Human Retinal Pigment Epithelium ARPE-19 Cells

Chang

Chen

et al. 2021

Pharmaceuticals

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This study investigated the regulatory role of microRNA 100 (miR-100) in hydrogen peroxide (H2O2)-induced apoptosis of human retinal pigment epithelial ARPE-19 cells. H2O2 induced oxidative cell death of cultured ARPE-19 cells was measured by cytotoxicity assay. qRT-PCR was used to quantify cytosolic and extracellular contents of miR-100. Kinase and miR-100 inhibition treatments were applied to determine the regulatory signaling pathways involved in cell death regulation. H2O2 dose-dependently reduced viability of ARPE-19 cells and simultaneously upregulated miR-100 levels in both cytosolic and extracellular compartments. Western blotting detection indicated that H2O2 elicited hyperphosphorylation of PI3K/Akt, ERK1/2, JNK, p38 MAPK, and p65 NF-κB. Further kinase inhibition experiments demonstrated that PI3K, p38 MAPK, and NF-κB activities were involved in oxidative-stress-induced miR-100 upregulation in ARPE-19 cells, while blockade of PI3K, JNK, and NF-κB signaling significantly attenuated the oxidative cell death. Intriguingly, MiR-100 antagomir treatment exerted a cytoprotective effect against the H2O2-induced oxidative cell death through attenuating the oxidation-induced AMPK hyperphosphorylation, restoring cellular mTOR and p62/SQSTM1 levels and upregulating heme oxygenase-1 expression. These findings support that miR-100 at least in part mediates H2O2-induced cell death of ARPE-19 cells and can be regarded as a preventive and therapeutic target for retinal degenerative disease.

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“…In such a way, derived factors of the microenvironment push tumor cells to induce EMT (5). In addition, TMEderived factors and their effects on EMT have an insightful part in the literature.…”

Section: Contextmentioning

confidence: 99%

Tumor Microenvironment: Involved Factors and Signaling Pathways in Epithelial-Mesenchymal Transition

Ghaderi

Niknejad

2021

Int J Cancer Manag

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Context: Metastasis is a main cause of death in patients with cancer, whereby tumor cells withdraw from the primary site of the tumor mass and produce secondary tumor mass in new sites. Primary tumor cells depart collectively and individually to invade closed and distant sites. Evidence Acquisition: This review considers TME-derived factors that actuate signaling pathways to induce epithelial-mesenchymal transition (EMT). National Center for Biotechnology Information (NCBI) was the main resource. Google Scholar and Scopus were other databases for finding articles. Keywords that were inserted into the search box of databases to identify related articles were ‘metastasis’, ‘invasion’, ‘epithelial-mesenchymal transition’, ‘EMT’, ‘tumor microenvironment’, ‘TME’, ‘TME cells’, and ‘signaling pathway in EMT’. Titles and abstracts of the articles were studied to choose the right articles. Finally, 100 articles were selected to study in detail and use as references. Results: EMT is a type of metastasis that deprives epithelial single-cells of their characteristic features and acquires mesenchymal features facilitating the departure from the primary tumor mass. During EMT, cell-adhesion and apical-basal polarity rapture and cells obtain movement capability. The tumor microenvironment (TME) leads EMT through secretion factors and signaling pathways. As a result of activating these pathways, transcription factors that abolish epithelial gene expressions and augment mesenchymal gene expression are induced. Conclusions: In this review, recent research published in TME and EMT fields were highlighted and critically appraised. Effect of factors-derived TME cells on EMT were manifested that propose favorite targets for a therapeutic goal to inhibit metastasis. However, data about the effect of the combination of TME cells on metastasis have a small part in the literature.

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Exosomes mediate an epithelial‐mesenchymal transition cascade in retinal pigment epithelial cells: Implications for proliferative vitreoretinopathy

Cited by 29 publications

References 63 publications

Proteomic profile of mesothelial exosomes isolated from peritoneal dialysis effluent of children with focal segmental glomerulosclerosis

Proteomic profile of mesothelial exosomes isolated from peritoneal dialysis effluent of children with focal segmental glomerulosclerosis

MicroRNA-100 Mediates Hydrogen Peroxide-Induced Apoptosis of Human Retinal Pigment Epithelium ARPE-19 Cells

Tumor Microenvironment: Involved Factors and Signaling Pathways in Epithelial-Mesenchymal Transition

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