MiR‐218 regulated cardiomyocyte differentiation and migration in mouse embryonic stem cells by targeting PDGFRα

Xu, Tingting; Liu, Nuoya; Shao, Ying; Huang, Yujie; Zhu, Danyan

doi:10.1002/jcb.27721

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…Overexpression of miR-218 in zebrafish embryos can inhibit the normal development of heart [20, 21]. Overexpression of miR-218 can also inhibit the differentiation of mouse embryonic stem cells into mesoderm and cardiomyocytes [22]. Therefore, we speculate that miR-218 is associated with MI.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of microRNA-218 is cardioprotective against cardiac fibrosis and cardiac function impairment in myocardial infarction by binding to MITF

Qian

Pan

Shi

et al. 2019

Aging

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Objective: This study is intended to figure out the function of microRNA-218 (miR-218) together with microphthalmia-associated transcription factor (MITF) on the cardiac fibrosis and cardiac function impairment in rat models of myocardial infarction (MI). Results: The rats with MI exhibited cardiac function impairment, cardiac fibrosis, oxidative stress, cardiomyocyte apoptosis, as well as inflammatory injury. Additionally, upregulated miR-218 and downregulated MITF were detected in cardiac tissues of MI rats. MI rats injected with miR-218 inhibitors or overexpressed MITF exhibited elevated MITF expression, improved cardiac function, and diminished pathological damages, infarct size, cardiomyocyte apoptosis, cardiac fibrosis, oxidative stress as well as inflammatory injury in cardiac tissues. Furthermore, downregulated miR-218 and MITF aggravated the conditions than downregulation of miR-218 alone in MI rats. Methods: MI models were performed in rats, and then the rats were injected with miR-218 inhibitors and/or MITF overexpression plasmid to elucidate the role of miR-218 and/or MITF on the cardiac function, pathological damage, cardiac fibrosis, angiogenesis, oxidative stress and inflammatory injury of cardiac tissues in MI rats by performing a series of assays. Conclusion: Collectively, we found that the suppression of miR-218 alleviates cardiac fibrosis and cardiac function impairment, and stimulates angiogenesis in MI rats through inhibiting MITF.

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Section: Introductionmentioning

confidence: 99%

Downregulation of microRNA-218 is cardioprotective against cardiac fibrosis and cardiac function impairment in myocardial infarction by binding to MITF

Qian

Pan

Shi

et al. 2019

Aging

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“…Our findings suggest that miR-140-5p can limit the suppression of adipogenesis-related gene expression and intracellular lipid accumulation by PDGFRα, thus contributing to adipogenesis. Consistent with this idea, PDGFRα is involved in the differentiation of cardiomyocyte differentiation (Xu et al, 2019). However, the signaling pathway in response to PDGFRα activation is still largely unknown, and thus the molecular processes regulating the expression and function of adipogenesis-related genes remain to be further investigated in future research.…”

Section: Discussionmentioning

confidence: 85%

microRNA-140 Regulates PDGFRα and Is Involved in Adipocyte Differentiation

Yan

Yuan

Luo

et al. 2022

Front. Mol. Biosci.

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In recent years, the studies of the role of microRNAs in adipogenesis and adipocyte development and the corresponding molecular mechanisms have received great attention. In this work, we investigated the function of miR-140 in the process of adipogenesis and the molecular pathways involved, and we found that adipogenic treatment promoted the miR-140-5p RNA level in preadipocytes. Over-expression of miR-140-5p in preadipocytes accelerated lipogenesis along with adipogenic differentiation by transcriptional modulation of adipogenesis-linked genes. Meanwhile, silencing endogenous miR-140-5p dampened adipogenesis. Platelet-derived growth factor receptor alpha (PDGFRα) was shown to be a miR-140-5p target gene. miR-140-5p over-expression in preadipocyte 3T3-L1 diminished PDGFRα expression, but silencing of miR-140-5p augmented it. In addition, over-expression of PDGFRα suppressed adipogenic differentiation and lipogenesis, while its knockdown enhanced these biological processes of preadipocyte 3T3-L1. Altogether, our current findings reveal that miR-140-5p induces lipogenesis and adipogenic differentiation in 3T3-L1 cells by targeting PDGFRα, therefore regulating adipogenesis. Our research provides molecular targets and a theoretical basis for the treatment of obesity-related metabolic diseases.

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“… 36 , 37 On the other hand, other groups have published that PDGFRα is important for stem/progenitor cell differentiation, in particular into α‐SMA‐expressing cells or fibroblasts. 13 , 38 , 39 , 40 These putative conflicting roles of PDGFRα might originate from the type of progenitor/stem cells used. We previously showed that CD34 + /PDGFRα + /PW1 + cells differentiate toward terminally differentiated smooth muscle myosin heavy chain + SMCs, 3 which might not be the case for the stem cells used in other studies.…”

Section: Discussionmentioning

confidence: 99%

Platelet‐Derived Growth Factor Receptor Type α Activation Drives Pulmonary Vascular Remodeling Via Progenitor Cell Proliferation and Induces Pulmonary Hypertension

Solinc

Raimbault-Machado

Dierick

et al. 2022

JAHA

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Background Platelet‐derived growth factor is a major regulator of the vascular remodeling associated with pulmonary arterial hypertension. We previously showed that protein widely 1 (PW1 + ) vascular progenitor cells participate in early vessel neomuscularization during experimental pulmonary hypertension (PH) and we addressed the role of the platelet‐derived growth factor receptor type α (PDGFRα) pathway in progenitor cell‐dependent vascular remodeling and in PH development. Methods and Results Remodeled pulmonary arteries from patients with idiopathic pulmonary arterial hypertension showed an increased number of perivascular and vascular PW1 + cells expressing PDGFRα. PW1 nLacZ reporter mice were used to follow the fate of pulmonary PW1 + progenitor cells in a model of chronic hypoxia–induced PH development. Under chronic hypoxia, PDGFRα inhibition prevented the increase in PW1 + progenitor cell proliferation and differentiation into vascular smooth muscle cells and reduced pulmonary vessel neomuscularization, but did not prevent an increased right ventricular systolic pressure or the development of right ventricular hypertrophy. Conversely, constitutive PDGFRα activation led to neomuscularization via PW1 + progenitor cell differentiation into new smooth muscle cells and to PH development in male mice without fibrosis. In vitro, PW1 + progenitor cell proliferation, but not differentiation, was dependent on PDGFRα activity. Conclusions These results demonstrate a major role of PDGFRα signaling in progenitor cell–dependent lung vessel neomuscularization and vascular remodeling contributing to PH development, including in idiopathic pulmonary arterial hypertension patients. Our findings suggest that PDGFRα blockers may offer a therapeutic add‐on strategy to combine with current pulmonary arterial hypertension treatments to reduce vascular remodeling. Furthermore, our study highlights constitutive PDGFRα activation as a novel experimental PH model.

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MiR‐218 regulated cardiomyocyte differentiation and migration in mouse embryonic stem cells by targeting PDGFRα

Cited by 8 publications

References 35 publications

Downregulation of microRNA-218 is cardioprotective against cardiac fibrosis and cardiac function impairment in myocardial infarction by binding to MITF

Downregulation of microRNA-218 is cardioprotective against cardiac fibrosis and cardiac function impairment in myocardial infarction by binding to MITF

microRNA-140 Regulates PDGFRα and Is Involved in Adipocyte Differentiation

Platelet‐Derived Growth Factor Receptor Type α Activation Drives Pulmonary Vascular Remodeling Via Progenitor Cell Proliferation and Induces Pulmonary Hypertension

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