MiR‐20a regulates the PRKG1 gene by targeting its coding region in pulmonary arterial smooth muscle cells

Zeng, Yan; Pan, Yongjie; Liu, Hongtai; Kang, Kang; Wu, Yike; Hui, Gang; Peng, Weiwen; Ramchandran, Ramaswamy; Raj, J. Usha; Gou, Deming

doi:10.1016/j.febslet.2014.10.040

Cited by 21 publications

(13 citation statements)

References 45 publications

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“…RT-qPCR (Bio-Rad iQ SYBR Green) was performed to analyze relative gene expression of PKG. According to the standard protocol for SYBR Green, the following primers were utilized: PKG: 5-CCG AAT TCT GTA TTT CTC TTA CCT GCT TC-3 (forward), CAC ACT AGT GGA CTC AGT TTA ATT TGT GG (reverse) [28]. Primers utilized for SYBR Green, were synthetized by Integrated DNA Technologies.…”

Section: Methodsmentioning

confidence: 99%

Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells

Samuel

Zhang

Tang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC. Methods: Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours). Nitric oxide (NO) production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh) and sodium nitroprusside (SNP). Results: Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC. Conclusion: Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation.

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Section: Methodsmentioning

confidence: 99%

Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells

Samuel

Zhang

Tang

et al. 2017

Cell Physiol Biochem

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“…[15]. PASMCs at passage 3 or 4 were used for experiments, and the contractile phenotype was confirmed by the determination of contractile marker genes expression, such as a-SMA and SM22 [16]. Growth factors including PDGFBB, AngII, TGF-b, IGF, VEGF, ET-1, PDGFAA and FGF were obtained from R&D Systems.…”

Section: Methodsmentioning

confidence: 99%

“…There is now accumulating evidence suggesting that microRNAs (miRNAs), a class of small endogenous non-coding RNA, can be essential in regulating PASMCs function [10–16]. MiRNAs are known to negatively regulate gene expression by mainly interacting with the 3′-untranslated region (UTR) of their target mRNAs [10–12].…”

Section: Introductionmentioning

confidence: 99%

MiR-328 targeting PIM-1 inhibits proliferation and migration of pulmonary arterial smooth muscle cells in PDGFBB signaling pathway

et al. 2016

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MicroRNAs (miRNAs) have been recognized to mediate PDGF-induced cell dysregulation, but their exact functions remain to be elucidated. By using a sensitive S-Poly(T) Plus qRT-PCR method, the expression profiling of 1,078 miRNAs were investigated in pulmonary artery smooth muscle cells (PASMCs) with or without PDGFBB stimulation. MiR-328 was found as a prominent down-regulated miRNA, displaying a specific dose- and time-dependent downregulation upon PDGFBB exposure. Functional analyses revealed that miR-328 could inhibit PASMCs proliferation and migration both with and without PDGFBB treatment. The Ser/Thr-protein kinase-1 (PIM-1) was identified as a direct target of miR-328, and functionally confirmed by a rescue experiment. In addition, the decrease of miR-328 by PDGFBB might be due to the increased expression of DNA methylation transferase 1 (DNMT1) and DNA methylation. Finally, serum miR-328 level was downregulated in PAH patients associated with congenital heart disease (CHD- PAH). Overall, this study provides critical insight into fundamental regulatory mechanism of miR-328 in PDGFBB-activited PASMCs via targeting PIM- 1, and implies the potential of serum miR-328 level as a circulating biomarker for CHD- PAH diagnosis.

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“…Freedman suggested that GUCY1A3 mutations were related to thrombosis (53). Zeng et al indicated that miR-20a regulates the PRKG1 gene, thereby promoting the proliferation, and contributes to thrombosis (54). TNF receptor superfamily members 10B, 10C, 10D and TNFSF10 linked to inflammation and coagulation and contribute to VTE (55).…”

Section: Discussionmentioning

confidence: 99%

Identification of potential drug targets based on a computational biology algorithm for venous thromboembolism

Xie

Chen

et al. 2016

International Journal of Molecular Medicine

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Venous thromboembolism (VTE) is a common, fatal and frequently recurrent disease. Changes in the activity of different coagulation factors serve as a pathophysiological basis for the recurrent risk of VTE. Systems biology approaches provide a better understanding of the pathological mechanisms responsible for recurrent VTE. In this study, a novel computational method was presented to identify the recurrent risk modules (RRMs) based on the integration of expression profiles and human signaling network, which hold promise for achieving new and deeper insights into the mechanisms responsible for VTE. The results revealed that the RRMs had good classification performance to discriminate patients with recurrent VTE. The functional annotation analysis demonstrated that the RRMs played a crucial role in the pathogenesis of VTE. Furthermore, a variety of approved drug targets in the RRM M5 were related to VTE. Thus, the M5 may be applied to select potential drug targets for combination therapy and the extended treatment of VTE.

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MiR‐20a regulates the PRKG1 gene by targeting its coding region in pulmonary arterial smooth muscle cells

Cited by 21 publications

References 45 publications

Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells

Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells

MiR-328 targeting PIM-1 inhibits proliferation and migration of pulmonary arterial smooth muscle cells in PDGFBB signaling pathway

Identification of potential drug targets based on a computational biology algorithm for venous thromboembolism

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