Negative feedback regulation between microRNA let-7g and LOX-1 mediated hypoxia-induced PASMCs proliferation

Zhang, Weifang; Zhu, Tiantian; Xiong, You-Wen; Xiong, Aizhen; Ge, Xinlan; Hu, Chang-Ping; Zhang, Zheng

doi:10.1016/j.bbrc.2017.01.073

Cited by 15 publications

(17 citation statements)

References 28 publications

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“…In addition, P27 and TIMP3 expressions were both down-regulated in PASMCs under hypoxic condition and were reversed by miR-222 inhibitor. These data provide evidence indicating that miR-222 inhibition may exert beneficial effect in reducing PASMC proliferation in pulmonary hypertension related to hypoxic conditions such as chronic obstructive pulmonary disease and interstitial lung disease [38, 39]. …”

Section: Discussionmentioning

confidence: 99%

MicroRNA-222 Promotes the Proliferation of Pulmonary Arterial Smooth Muscle Cells by Targeting P27 and TIMP3

Xü¹,

Bei²,

Shen³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Aberrant vascular smooth muscle cell (VSMC) proliferation plays an important role in the development of pulmonary artery hypertension (PAH). Dysregulated microRNAs (miRNAs, miRs) have been implicated in the progression of PAH. miR-222 has a pro-proliferation effect on VSMCs while it has an anti-proliferation effect on vascular endothelial cells (ECs). As the biological function of a single miRNA could be cell-type specific, the role of miR-222 in pulmonary artery smooth muscle cell (PASMC) proliferation is not clear and deserves to be explored. Methods: PASMCs were transfected with miR-222 mimic or inhibitor and PASMC proliferation was determined by Western blot for PCNA, Ki-67 and EdU staining, and cell number counting. The target genes of miR-222 including P27 and TIMP3 were determined by luciferase assay and Western blot. In addition, the functional rescue experiments were performed based on miR-222 inhibitor and siRNAs to target genes. Results: miR-222 mimic promoted PASMC proliferation while miR-222 inhibitor decreased that. TIMP3 was identified to be a direct target gene of miR-222 based on luciferase assay. Meanwhile, P27 and TIMP3 were up-regulated by miR-222 inhibitor and down-regulated by miR-222 mimic. Moreover, P27 siRNA and TIMP3 siRNA could both attenuate the anti-proliferation effect of miR-222 inhibitor in PASMCs, supporting that P27 and TIMP3 are at least partially responsible for the regulatory effect of miR-222 in PASMCs. Conclusion: miR-222 promotes PASMC proliferation at least partially through targeting P27 and TIMP3.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-222 Promotes the Proliferation of Pulmonary Arterial Smooth Muscle Cells by Targeting P27 and TIMP3

Xü¹,

Bei²,

Shen³

et al. 2017

Cell Physiol Biochem

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“…Zhang et al . () demonstrated that hypoxia exposure (10%, 3 weeks) significantly increased LOX‐1 protein expression in PAs via the downregulation of miRNA let‐7g. Transgenic mice overexpressing LOX‐1 did not show any pulmonary vascular remodelling and phenotypes; however, these mice were more susceptible to developing HPH due to excess ROS production in PAs (Ogura et al .…”

Section: Vascular Function In Dyslipidaemiamentioning

confidence: 98%

Pulmonary vascular dysfunction in metabolic syndrome

Willson

Watanabe

Tsuji‐Hosokawa

2018

The Journal of Physiology

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Metabolic syndrome is a critically important precursor to the onset of many diseases, such as cardiovascular disease, and cardiovascular disease is the leading cause of death worldwide. The primary risk factors of metabolic syndrome include hyperglycaemia, abdominal obesity, dyslipidaemia, and high blood pressure. It has been well documented that metabolic syndrome alters vascular endothelial and smooth muscle cell functions in the heart, brain, kidney and peripheral vessels. However, there is less information available regarding how metabolic syndrome can affect pulmonary vascular function and ultimately increase an individual's risk of developing various pulmonary vascular diseases, such as pulmonary hypertension. Here, we review in detail how metabolic syndrome affects pulmonary vascular function.

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“…For HE staining, the fixed lungs were embedded in paraffin and then cut into approximately 5 μ m thick sections by microtome. HE staining of right lung was conducted in accordance to the same method used in our previous study [ 6 ].…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies have linked calpain with a variety of diseases, such as Alzheimer's and Parkinson's diseases, cancer, diabetes, atherosclerosis, and PH [ 5 ]. In hypoxia and monocrotaline-induced PH of mice and rats, the expression of calpain-1/2/4 in the lung tissues and pulmonary arteries was significantly increased [ 6 – 8 ]. Research focusing on the role of calpain-2 in hypoxia-induced PH becomes a meaningful work.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-137 Inhibited Hypoxia-Induced Proliferation of Pulmonary Artery Smooth Muscle Cells by Targeting Calpain-2

Zhu

Yao

et al. 2021

BioMed Research International

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The proliferation of pulmonary artery smooth muscle cells (PASMCs) is an important cause of pulmonary vascular remodeling in pulmonary hypertension (PH). It has been reported that miR-137 inhibits the proliferation of tumor cells. However, whether miR-137 is involved in PH remains unclear. In this study, male Sprague-Dawley rats were subjected to 10% O2 for 3 weeks to establish PH, and rat primary PASMCs were treated with hypoxia (3% O2) for 48 h to induce cell proliferation. The effect of miR-137 on PASMC proliferation and calpain-2 expression was assessed by transfecting miR-137 mimic and inhibitor. The effect of calpain-2 on PASMC proliferation was assessed by transfecting calpain-2 siRNA. The present study found for the first time that miR-137 was downregulated in pulmonary arteries of hypoxic PH rats and in hypoxia-treated PASMCs. miR-137 mimic inhibited hypoxia-induced PASMC proliferation and upregulation of calpain-2 expression in PASMCs. Furthermore, miR-137 inhibitor induced the proliferation of PASMCs under normoxia, and knockdown of calpain-2 mRNA by siRNA significantly inhibited hypoxia-induced proliferation of PASMCs. Our study demonstrated that hypoxia-induced downregulation of miR-137 expression promoted the proliferation of PASMCs by targeting calpain-2, thereby potentially resulting in pulmonary vascular remodeling in hypoxic PH.

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Negative feedback regulation between microRNA let-7g and LOX-1 mediated hypoxia-induced PASMCs proliferation

Cited by 15 publications

References 28 publications

MicroRNA-222 Promotes the Proliferation of Pulmonary Arterial Smooth Muscle Cells by Targeting P27 and TIMP3

MicroRNA-222 Promotes the Proliferation of Pulmonary Arterial Smooth Muscle Cells by Targeting P27 and TIMP3

Pulmonary vascular dysfunction in metabolic syndrome

MicroRNA-137 Inhibited Hypoxia-Induced Proliferation of Pulmonary Artery Smooth Muscle Cells by Targeting Calpain-2

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