MiR-21 promotes ECM degradation through inhibiting autophagy via the PTEN/akt/mTOR signaling pathway in human degenerated NP cells

Wang, Wenjun; Yang, Wei; Ouyang, Zigen; Xue, Jing; Li, Xuelin; Zhang, Jian; He, Wen-Si; Chen, Wenkang; Yan, Yongping; Wang, Cheng

doi:10.1016/j.biopha.2018.01.154

Cited by 68 publications

(52 citation statements)

References 41 publications

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“…A comparison of miRNAs detected in the NPCE samples to the most overlapping miRNAs families in the AH. A, The Venn diagram adapted from Hari Jayaram et al depicts the overlap of human AH miRNAs detected in five studies. B, Venn diagram displays the total number of miRNAs detected in the EV samples isolated from NPCE cell culture medium (n = 2) compared to the most overlapping AH miRNAs families from the published datay .…”

Section: Resultsmentioning

confidence: 99%

“…A, The Venn diagram adapted from Hari Jayaram et al depicts the overlap of human AH miRNAs detected in five studies. B, Venn diagram displays the total number of miRNAs detected in the EV samples isolated from NPCE cell culture medium (n = 2) compared to the most overlapping AH miRNAs families from the published datay . C, Expression levels of 27 miRNAs identified in EVs derived by NPCE cell line overlapping with those observed within the AH…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, miR‐21 was shown to target TIMP3, a tissue inhibitor of MMPs, promoting MMP activity, leading to degradation of ECM . Another recent study on human tissues suggests that miR‐21 promotes ECM degradation through inhibiting autophagy via the PTEN/Akt/mTOR signalling pathway …”

Section: Discussionmentioning

confidence: 99%

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Extracellular vesicle‐mediated crosstalk between NPCE cells and TM cells result in modulation of Wnt signalling pathway and ECM remodelling

Lerner

Schreiber‐Avissar

Beit‐Yannai

2020

J Cellular Molecular Medi

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Primary open-angle glaucoma is a leading cause of irreversible blindness, often associated with increased intraocular pressure. Extracellular vesicles (EVs) carry a specific composition of proteins, lipids and nucleotides have been considered as essential mediators of cell-cell communication. Their potential impact for crosstalk between tissues responsible for aqueous humour production and out-flow is largely unknown.The study objective was to investigate the effects of EVs derived from non-pigmented ciliary epithelium (NPCE) primary cells on the expression of Wnt proteins in a human primary trabecular meshwork (TM) cells and define the mechanism underlying exosome-mediated regulation that signalling pathway. Consistent with the results in TM cell line, EVs released by both primary NPCE cells and NPCE cell line showed diminished pGSK3β phosphorylation and decreased cytosolic levels of β-catenin in primary TM cells. At the molecular level, we showed that NPCE exosome treatment downregulated the expression of positive GSKβ regulator-AKT protein but increased the levels of GSKβ negative regulator-PP2A protein in TM cells. NPCE exosome protein analysis revealed 584 miRNAs and 182 proteins involved in the regulation of TM cellular processes, including WNT/β-catenin signalling pathway, cell adhesion and extracellular matrix deposition. We found that negative modulator of Wnt signalling miR-29b was abundant in NPCE exosomal samples and treatment of TM cells with NPCE EVs significantly decreased COL3A1 expression. Suggesting that miR-29b can be responsible for decreased levels of WNT/β-catenin pathway. Overall, this study highlights a potential role of EVs derived from NPCE cells in modulating ECM proteins and TM canonical Wnt signalling. K E Y W O R D S exosomes, extracellular matrix, extracellular vesicles, non-pigmented ciliary epithelium, primary open-angle glaucoma, trabecular meshwork, Wnt | 4647 LERNER Et aL.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Extracellular vesicle‐mediated crosstalk between NPCE cells and TM cells result in modulation of Wnt signalling pathway and ECM remodelling

Lerner

Schreiber‐Avissar

Beit‐Yannai

2020

J Cellular Molecular Medi

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“…Previous investigations have shown that miRNAs played important roles in physiological and pathological processes, including cell cycle regulation [1], cell differentiation [1] in ammatory responses [2], apoptosis [3] and extracellular matrix (ECM) degradation [4]. Upgraded serum miRNA-204 (miR-204) levels have been regarded as associated with insulinoma [5], acute lymphocytic leukemia [6], human breast cancer [7] and other tumors [8].…”

Section: Introductionmentioning

confidence: 99%

Serum microRNA-204 Levels are Associated with Long-Term Cardiovascular Diseases Risk Using Framingham Risk Score in Patients with Type 2 Diabetes: Results From an Observational Study

Wang

Ding

Pei

et al. 2020

Preprint

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Background: The basic studies have demonstrated that microRNA-204 (miRNA-204) was involved in the process of atherosclerosis and vascular calcification. However, the value of miRNA-204 as a predictive biomarker for cardiovascular disease (CVD) is still controversial. The purpose of the present study was to evaluate the association between circulating miRNA-204 level and the 10-year cardiovascular disease risk score, Framingham risk score (FRS).Method: The subjects consecutively enrolled 194 patients with type 2 diabetes mellitus without cardiovascular disease at Anzhen Hospital from January 2015 to September 2016. We used the Framingham Risk Score (FRS) to evaluate the risk of cardiovascular disease. Circulating miRNA-204 levels were measured by quantitative Real-Time polymerase chain reaction (qRT-PCR).Result: The circulating miRNA-204 levels were significantly lower in high risk group of CVD (FRS > 20%) of patients (0.49 ± 0.13) compared with that in low risk group (FRS < 10%) and intermediate risk group (FRS = 10%-20%) (0.87 ± 0.19, 0.75 ± 0.25, Respectively, p < 0.001). FRS was negatively correlated with miR-204 levels (r=-0.421, p < 0.001). According to multivariate logistic analyses, miRNA-204 levels were still significantly and independently associated with the high risk of CVD after adjusting the conventional risk factor. Receiver-operating characteristic curve (ROC) analysis also showed that circulating miRNA-204 level can predict the high risk of CVD, and the specificity was higher than traditional risk factors SBP and protective factor HDL-C of CVD.Conclusion: Our study demonstrated that patients with lower circulating miRNA-204 levels were at a high risk for the progression of CVD. After adjustment for potential confounders, miRNA-204 was independently associated with CVD in patients with T2DM.

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“…12 miR-21 is involved in a number of complex signaling pathways that are still being revealed, but one important pathway is the PTEN/Akt/mTOR signaling pathway, which has been shown to be important in extracellular matrix degradation. 13 This pathway involves phosphatidylinositol 3-kinase (PI3K), chromosome 10 neutropenic protein phosphatase (PTEN), protein kinase B (Akt), and mammalian target of rapamycin (mTOR), and it may also be important in fibroblast proliferation. The expression of PTEN, a direct target of miR-21, has been shown to be lower in keloid tissues than in adjacent normal skin tissues.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-21 may be involved in the therapeutic effects of Galla chinensis ointment on keloid

et al. 2020

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Objective: Galla chinensis ointment can inhibit the proliferation of keloid fibroblasts and decrease keloid formation. We investigated whether Galla chinensis ointment inhibits keloid fibroblast proliferation through expression of microRNA-21, phosphorylated (p)-phosphatidylinositol 3-kinase (p-PI3K), chromosome 10 neutropenic protein phosphatase (PTEN), protein kinase B (p-Akt), and mammalian target of rapamycin (p-mTOR). Methods: A keloid mouse model and human keloid-derived fibroblasts were developed and treated with Galla chinensis. Immunohistochemistry, western blot, and reverse transcription-PCR were used to detect miR-21, PI3K, PTEN, Akt, and mTOR in keloid tissues. Results: p-Akt and p-mTOR were highly expressed in the control group, PTEN was highly expressed in the treatment group, and p-PI3K was highly expressed in keloid tissue in both groups. Galla chinensis reduced miR-21 expression and increased PTEN mRNA expression in keloid fibroblasts compared with the control group, resulting in increased PTEN protein and decreased p-Akt and p-mTOR protein. Galla chinensis had no effect on p-PI3K. Conclusion: Galla chinensis might inhibit proliferation of keloid fibroblasts by upregulating PTEN, thus inhibiting expression of miR-21 and downregulating p-Akt and p-mTOR expression. These results confirm the effect of Galla chinensis ointment on fibroblasts and suggest that it could be used to manage keloids clinically.

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MiR-21 promotes ECM degradation through inhibiting autophagy via the PTEN/akt/mTOR signaling pathway in human degenerated NP cells

Cited by 68 publications

References 41 publications

Extracellular vesicle‐mediated crosstalk between NPCE cells and TM cells result in modulation of Wnt signalling pathway and ECM remodelling

Extracellular vesicle‐mediated crosstalk between NPCE cells and TM cells result in modulation of Wnt signalling pathway and ECM remodelling

Serum microRNA-204 Levels are Associated with Long-Term Cardiovascular Diseases Risk Using Framingham Risk Score in Patients with Type 2 Diabetes: Results From an Observational Study

MicroRNA-21 may be involved in the therapeutic effects of Galla chinensis ointment on keloid

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