<i>MicroRNA-9</i> inhibits high glucose-induced proliferation, differentiation and collagen accumulation of cardiac fibroblasts by down-regulation of TGFBR2

Li, Jiaxin; Dai, Yue; Su, Zhendong; Wei, Guoqian

doi:10.1042/bsr20160346

Cited by 23 publications

(14 citation statements)

References 34 publications

(40 reference statements)

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“…In cardiac fibroblast, miR-9 alleviated proliferation as well as collagen by regulating transforming growth factor b receptor type II (TGFBR2) [33]. Similar results can be seen in our study that transfection with miR-9 inhibitor promoted cell proliferation and collagen production, which was consistent with the previous finding [33]. However, in our study, the regulating relationship between baicalein and miR-9 was validated for the first time.…”

Section: Discussionsupporting

confidence: 92%

Baicalein inhibits proliferation and collagen synthesis of mice fibroblast cell line NIH/3T3 by regulation of miR-9/insulin-like growth factor-1 axis

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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The aberrant scar is a challenging problem. Baicalein has effects in attenuating hypertrophic scar formation. Herein, the roles of baicalein in NIH-3T3 were obtained. Cells were treated by baicalein. CCK-8 method and western blot were used to detect cell viability and proliferation-related factors. Furthermore, collagen 1, collagen 3 and a-SMA expression were detected by qRT-PCR and western blot. Besides, total soluble collagen was detected by Sircol assay. In addition, the levels of NF-jB and Wnt/b-catenin signal pathways related factors were determined by western blot. The relationship between miR-9 and insulin-like growth factor (IGF)-1 were tested by luciferase reporter assay, qRT-PCR and western blot. We found baicalein cell restrained proliferation and collagen production. Besides, baicalein increased expression of miR-9 and further experiments validated that transfection with miR-9 inhibitor reversed the results led by baicalein. Moreover, baicalein decreased the phosphorylation of pathway-related proteins while transfection with miR-9 inhibitor revised this result. Otherwise, IGF-1 was authenticated as a target of miR-9 and si-IGF-1 reversed the miR-9 inhibitor-induced change in cell proliferation and collagen production. In conclusion, baicalein restrained cell proliferation and collagen production by regulating miR-9/IGF-1 axis through NF-jB and Wnt/b-catenin signal pathways. HIGHLIGHTS:1. Baicalein restrains NIH/3T3 cell proliferation and collagen production. 2. Baicalein restrains NF-jB and Wnt/b-catenin signal pathways. 3. IGF-1 is a target of miR-9. 4. Baicalein exerts its functions by regulating miR-9/IGF-1 axis. ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 92%

Baicalein inhibits proliferation and collagen synthesis of mice fibroblast cell line NIH/3T3 by regulation of miR-9/insulin-like growth factor-1 axis

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Therefore to develop a reliable 3D cardiac tissue model with increased physiological relevance, hESC-derived CMs were mixed with hESC-derived MSCs similar to those likely to be found in human cardiac tissue. In consideration of a report that cardiac fibroblasts account for 20% of total mass of the myocardium [28, 29] and the considerable variation of the ratio of cell numbers of fibroblasts in heart across studies [30], we tested various ratios of MSCs (5–20%), which are used as a source of fibroblasts in CM-MSC cardiac microtissues. Therefore, a single cell suspension of CMs was mixed at a 5–20% ratio of a single cell suspension of MSCs in round bottom 96-well ultra-low attachment plates to form cardiac microtissues called spheroids.…”

Section: Resultsmentioning

confidence: 99%

Modelling cardiac fibrosis using three-dimensional cardiac microtissues derived from human embryonic stem cells

Lee

Jung

et al. 2019

J Biol Eng

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Background Cardiac fibrosis is the most common pathway of many cardiac diseases. To date, there has been no suitable in vitro cardiac fibrosis model that could sufficiently mimic the complex environment of the human heart. Here, a three-dimensional (3D) cardiac sphere platform of contractile cardiac microtissue, composed of human embryonic stem cell (hESC)-derived cardiomyocytes (CMs) and mesenchymal stem cells (MSCs), is presented to better recapitulate the human heart. Results We hypothesized that MSCs would develop an in vitro fibrotic reaction in response to treatment with transforming growth factor-β1 (TGF-β1), a primary inducer of cardiac fibrosis. The addition of MSCs improved sarcomeric organization, electrophysiological properties, and the expression of cardiac-specific genes, suggesting their physiological relevance in the generation of human cardiac microtissue model in vitro. MSCs could also generate fibroblasts within 3D cardiac microtissues and, subsequently, these fibroblasts were transdifferentiated into myofibroblasts by the exogenous addition of TGF-β1. Cardiac microtissues displayed fibrotic features such as the deposition of collagen, the presence of numerous apoptotic CMs and the dissolution of mitochondrial networks. Furthermore, treatment with pro-fibrotic substances demonstrated that this model could reproduce key molecular and cellular fibrotic events. Conclusions This highlights the potential of our 3D cardiac microtissues as a valuable tool for manifesting and evaluating the pro-fibrotic effects of various agents, thereby representing an important step forward towards an in vitro system for the prediction of drug-induced cardiac fibrosis and the study of the pathological changes in human cardiac fibrosis. Electronic supplementary material The online version of this article (10.1186/s13036-019-0139-6) contains supplementary material, which is available to authorized users.

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“…Furthermore, some cis -elements in the mRNAs 3’-UTRs are also known to mediate the regulation of mRNA decay, such as PAT [29,30], ARE [31], iron-responsive element (IRE) [32], GRE [33], and MRE [34]. Many studies have demonstrated that the expression of TGFBR2 is modulated by MREs and their miRNAs in various cell types, such as miR-145 in vascular smooth muscle cells [35], miR-9-5p in hepatic stellate cells [36], miR-9 and miR-9-5p fibroblasts (HCFs) [6,37], miR-520e, miR-9-5p, and miR-135b in cancer cells [38,39,40]. Notably, miR-143 [23], miR-130a, miR-425, and miR-1306 [9] are known to target TGFBR2 in porcine GCs.…”

Section: Discussionmentioning

confidence: 99%

miR-1306 Mediates the Feedback Regulation of the TGF-β/SMAD Signaling Pathway in Granulosa Cells

Yang

Liu

et al. 2019

Cells

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Transforming growth factor-β receptor II (TGFBR2), the type II receptor of the TGF-β/SMA- and MAD-related protein (SMAD) signaling pathway, plays a crucial role in TGF-β signal transduction and is regulated by multiple factors. Nevertheless, the modulation of the non-coding RNA involved in the process of TGFBR2 expression in ovaries is not well studied. In our study, we isolated and characterized the 3′-untranslated region (UTR) of the porcine TGFBR2 gene and microRNA-1306 (miR-1306) was identified as the functional miRNA that targets TGFBR2 in porcine granulosa cells (GCs). Functional analysis showed that miR-1306 promotes apoptosis of GCs as well as attenuating the TGF-β/SMAD signaling pathway targeting and impairing TGFBR2 in GCs. Moreover, we identified the miR-1306 core promoter and found three potential SMAD4-binding elements (SBEs). Luciferase and chromatin immunoprecipitation (ChIP) assays revealed that the transcription factor SMAD4 directly binds to the miR-1306 core promoter and inhibits its transcriptional activity. Furthermore, the TGF-β/SMAD signaling pathway is modulated by SMAD4 positive feedback via inhibition of miR-1306 expression in GCs. Collectively, our findings provide evidence of an epigenetic mechanism that modulates as well as mediates the feedback regulation of the classical TGF-β/SMAD signaling pathway in GCs from porcine ovaries.

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MicroRNA-9 inhibits high glucose-induced proliferation, differentiation and collagen accumulation of cardiac fibroblasts by down-regulation of TGFBR2

Cited by 23 publications

References 34 publications

Baicalein inhibits proliferation and collagen synthesis of mice fibroblast cell line NIH/3T3 by regulation of miR-9/insulin-like growth factor-1 axis

Baicalein inhibits proliferation and collagen synthesis of mice fibroblast cell line NIH/3T3 by regulation of miR-9/insulin-like growth factor-1 axis

Modelling cardiac fibrosis using three-dimensional cardiac microtissues derived from human embryonic stem cells

miR-1306 Mediates the Feedback Regulation of the TGF-β/SMAD Signaling Pathway in Granulosa Cells

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