miR-21 enhances cardiac fibrotic remodeling and fibroblast proliferation via CADM1/STAT3 pathway

Cao, Wei; Shi, Peng; Ge, Jianjun

doi:10.1186/s12872-017-0520-7

Cited by 83 publications

(57 citation statements)

References 18 publications

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“…miR-21 upregulation in plasma has been proposed as an indicator for cardiac fibrotic remodeling in young diabetic patients. 35 miR-21 was also reported to prevent type 1 diabetes in mice; it is involved in a regulatory pathway of beta-cell death, where it decreases the level of PDCD4 protein that induces death of pancreatic beta cells, thereby and did not differ significantly between T1DM, controls and GCK-MODY patients from our profiling cohort.…”

Section: Takahashi Et Al Reported Higher Let-7g Expression In Pbmcs mentioning

confidence: 64%

“…Also, significantly higher levels of miR‐21 were previously reported in PBMCs and in plasma of T1DM patients. miR‐21 upregulation in plasma has been proposed as an indicator for cardiac fibrotic remodeling in young diabetic patients . miR‐21 was also reported to prevent type 1 diabetes in mice; it is involved in a regulatory pathway of beta‐cell death, where it decreases the level of PDCD4 protein that induces death of pancreatic beta cells, thereby potentially preventing T1DM .…”

Section: Discussionmentioning

confidence: 99%

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Temporal dynamics of serum let‐7g expression mirror the decline of residual beta‐cell function in longitudinal observation of children with type 1 diabetes

et al. 2018

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Background/Objective In type 1 diabetes mellitus (T1DM), the introduction of insulin is typically followed by a brief remission period, with subsequent gradual decline in beta‐cell function. Several studies described altered profile of circulating miRNAs (microRNAs) in T1DM patients and proposed them as biomarkers of associated pathologic processes. Hypothesis Serum miRNA expression profile reflects residual beta‐cell function and autoimmunity in T1DM. Subjects The profiling group included patients with: GCK‐MODY (N = 13), T1DM (N = 9), and 10 healthy controls. The longitudinal group included 34 patients with samples collected at diagnosis of T1DM and first, third, and fourth to eighth year since diagnosis. Methods We reanalyzed data from the profiling group for miRNAs differentially expressed between patients with T1DM, other types of diabetes and controls. Afterward, we shortlisted miRNAs on the basis of this reanalysis and literature review and quantified their expression with quantitative polymerase chain reaction. Additionally, we measured the levels of anti‐islet antibodies (islet cell antibodies, glutamic acid decarboxylase antibodies, IA2 antibodies, and ZnT8A) and C‐peptide concentrations across the four timepoints in the longitudinal group. Results miR‐24 and let‐7g serum expression differed significantly between GCK‐MODY, controls, and HbA1c‐matched T1DM patients; P < 0.05, false discovery rate < 0.05. Autoantibodies levels showed decreasing linear trend in repeated timepoints (all P < 0.0001). C‐peptide concentration peaked during the first year after diagnosis, corresponding to remission phase, and declined in consecutive measurements. This dynamic was evidenced for let‐7g expression levels (P = 0.0058). Conclusions The pattern of let‐7g expression change during the course of diabetes mirrors that of C‐peptide levels, hinting at this microRNA's association with the residual mass of the beta cells in patients with T1DM.

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Section: Takahashi Et Al Reported Higher Let-7g Expression In Pbmcs mentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Temporal dynamics of serum let‐7g expression mirror the decline of residual beta‐cell function in longitudinal observation of children with type 1 diabetes

et al. 2018

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“…Notably, recent studies reveal additional mechanisms underlying the role of miR‐21 in cardiac fibrosis. Cao et al reported that tumour suppressor cell adhesion molecule 1 (CADM1) is the potential target of miR‐21 and miR‐21 enhances cardiac fibrotic remodelling and fibroblast proliferation via targeting CADM1. Yuan et al found that miR‐21 promoted cardiac fibrosis after MI via targeting Smad7.…”

Section: Discussionmentioning

confidence: 99%

miR‐21 promotes cardiac fibroblast‐to‐myofibroblast transformation and myocardial fibrosis by targeting Jagged1

Zhou

Liu

et al. 2018

J Cellular Molecular Medi

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Myocardial fibrosis after myocardial infarction (MI) is a leading cause of heart diseases. MI activates cardiac fibroblasts (CFs) and promotes CF to myofibroblast transformation (CMT). This study aimed to investigate the role of miR‐21 in the regulation of CMT and myocardial fibrosis. Primary rat CFs were isolated from young SD rats and treated with TGF‐β1, miR‐21 sponge or Jagged1 siRNA. Cell proliferation, invasion and adhesion were detected. MI model was established in male SD rats using LAD ligation method and infected with recombinant adenovirus. The heart function and morphology was evaluated by ultrasonic and histological analysis. We found that TGF‐β1 induced the up‐regulation of miR‐21 and down‐regulation of Jagged1 in rat CFs. Luciferase assay showed that miR‐21 targeted 3′‐UTR of Jagged1 in rat CFs. miR‐21 sponge inhibited the transformation of rat CFs into myofibroblasts, and abolished the inhibition of Jagged1 mRNA and protein expression by TGF‐β1. Furthermore, these effects of miR‐21 sponge on rat CFS were reversed by siRNA mediated knockdown of Jagged1. In vivo, heart dysfunction and myocardial fibrosis in MI model rats were partly improved by miR‐21 sponge but were aggravated by Jagged1 knockdown. Taken together, these results suggest that miR‐21 promotes cardiac fibroblast‐to‐myofibroblast transformation and myocardial fibrosis by targeting Jagged1. miR‐21 and Jagged1 are potential therapeutic targets for myocardial fibrosis.

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“…Recently, miR-21 has been ascribed a crucial role in the regulation of cellular activity during physiological and pathological processes [31]. miR‑21 is widely expressed and has been found to be increased in organs and tissues which have suffered fibrogenesis or remodeling, including the heart [32], kidney [33], lung [34], asthmatic airways [35, 36], liver [37, 38], skin [39-41], and tumor tissue [42, 43]. Studies revealed that enhanced miR-21 expression is involved in the progression of lung fibrosis, and TGF-β1 plays an important role in mediating increased miR-21 expression [34, 44].…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

Zhu

et al. 2019

Int Arch Allergy Immunol

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Objectives: To characterize the epithelial-mesenchymal transition (EMT) in chronic rhinosinusitis with nasal polyps (CRSwNP) and to investigate the mechanism by which microRNA-21 (miR-21) regulates EMT in CRSwNP. Method: (1) Tissue experiments: Mucosa tissues were collected from 13 patients with CRSwNP and 12 patients with CRS without nasal polyps (CRSsNP), as well as 11 patients without CRS (controls). Protein localization and quantification were achieved by immunofluorescence staining and Western blotting, involving the epithelial marker protein E-cadherin and the mesenchymal marker proteins α-smooth muscle actin (α-SMA), fibronectin, and vimentin. Quantitative RT-PCR was used to detect the relative expression levels of miR-21 and TGF-β1 mRNAs. (2) Cellular experiments: Primary human nasal epithelial cells (PHNECs) treated with TGF-β1, or TGF-β1 with miR-21 inhibitor, or miR-21 mimics alone were observed for morphology changes under a phase-contrast microscope. The expression levels of epithelial/mesenchymal marker proteins were determined as aforementioned. PTEN and phosphorylated Akt were detected by Western blotting. Results: (1) Tissue experiments: Compared with the CRSsNP and control groups, the expression of E-cadherin was downregulated in the CRSwNP group, whereas the expression of TGF-β1, α-SMA, fibronectin, and vimentin was upregulated. The expression levels of miR-21 and TGF-β1 mRNAs in CRSwNP were significantly higher than those in CRSsNP and controls. (2) Cellular experiments: TGF-β1 induced EMT-like transformation in PHNECs, featured by changes in cell morphology and upregulation of mesenchymal proteins and miR-21. The miR-21 inhibitor, as well as the Akt-specific inhibitor, suppressed TGF-β1-induced EMT. Mechanically, downregulation of miR-21 resulted in increased PTEN and decreased Akt phosphorylation. Furthermore, overexpression of miR-21 had the opposite effects. Conclusions: Our findings suggest that the TGF-β1-miR-21-PTEN-Akt axis may contribute to the pathogenesis of CRSwNP. miR-21 might be a reliable target for treating nasal polyp genesis through EMT suppression. Moreover, miR-21 inhibitors could be a novel class of antipolyp drug that modulates PTEN expression and Akt activation. In addition, further investigation regarding the reason underlying miR-21 overexpression in CRSwNP could provide a molecular target for novel treatment strategies for nasal polyposis.

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miR-21 enhances cardiac fibrotic remodeling and fibroblast proliferation via CADM1/STAT3 pathway

Cited by 83 publications

References 18 publications

Temporal dynamics of serum let‐7g expression mirror the decline of residual beta‐cell function in longitudinal observation of children with type 1 diabetes

Temporal dynamics of serum let‐7g expression mirror the decline of residual beta‐cell function in longitudinal observation of children with type 1 diabetes

miR‐21 promotes cardiac fibroblast‐to‐myofibroblast transformation and myocardial fibrosis by targeting Jagged1

TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

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