miRNA‐34a promotes proliferation of human pulmonary artery smooth muscle cells by targeting PDGFRA

Wang, Peng; Xu, Jie; Hou, Zhi-ling; Wang, Fangfang; Song, Ye; Wang, Jiao; Zhu, Hui; Jin, Hongbo

doi:10.1111/cpr.12265

Cited by 58 publications

(39 citation statements)

References 46 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Pdgfra 3′ UTR is unusually long, characteristic of mRNAs subjected to tight post-transcriptional regulation and is predicted to be targeted by more than 50 conserved miRNAs 1 . Indeed, Pdgfra is an experimentally validated target for miR-34a in pulmonary artery smooth muscle and colon cancer cells and glioblastoma (Genovese et al, 2012; Li C. et al, 2015; Wang P. et al, 2016), miR-130a during mesodermal specification (Singh et al, 2015), miR-146b-5p in blood cells and hepatocellular carcinoma (Zhu et al, 2013; Zhai et al, 2014) and miR-140 during palatogenesis (Eberhart et al, 2008). Moreover, the Regazzi laboratory, in collaboration with ourselves, has very recently demonstrated that miR-34a targets Pdgfra in rat islet cells (Tugay et al, 2016).…”

Section: Mirnas and Disallowed Genesmentioning

confidence: 99%

MiRNAs in β-Cell Development, Identity, and Disease

2017

View full text Add to dashboard Cite

Pancreatic β-cells regulate glucose metabolism by secreting insulin, which in turn stimulates the utilization or storage of the sugar by peripheral tissues. Insulin insufficiency and a prolonged period of insulin resistance are usually the core components of type 2 diabetes (T2D). Although, decreased insulin levels in T2D have long been attributed to a decrease in β-cell function and/or mass, this model has recently been refined with the recognition that a loss of β-cell “identity” and dedifferentiation also contribute to the decline in insulin production. MicroRNAs (miRNAs) are key regulatory molecules that display tissue-specific expression patterns and maintain the differentiated state of somatic cells. During the past few years, great strides have been made in understanding how miRNA circuits impact β-cell identity. Here, we review current knowledge on the role of miRNAs in regulating the acquisition of the β-cell fate during development and in maintaining mature β-cell identity and function during stress situations such as obesity, pregnancy, aging, or diabetes. We also discuss how miRNA function could be harnessed to improve our ability to generate β-cells for replacement therapy for T2D.

show abstract

Section: Mirnas and Disallowed Genesmentioning

confidence: 99%

MiRNAs in β-Cell Development, Identity, and Disease

2017

View full text Add to dashboard Cite

show abstract

“…Tumor necrosis factor-α inhibits Pdgfrα transcription depending on cFos-YY1 complex formation and histone deacetylase activity [56]. Besides transcriptional control, PDGFRα mRNA level in hypoxia-exposed pulmonary artery smooth muscle cells could be downregulated by microRNA-34a (miR-34a) to impair cell proliferation and migration [57]. Interestingly, a recent study reported that miR-34a level is markedly elevated in a hyperoxiabased BPD mouse model to impair PDGFRα expression and MYF proliferation [58].…”

Section: Discussionmentioning

confidence: 99%

CPEB2-activated PDGFRα mRNA translation contributes to myofibroblast proliferation and pulmonary alveologenesis

et al. 2020

View full text Add to dashboard Cite

Background: Alveologenesis is the final stage of lung development to form air-exchanging units between alveoli and blood vessels. Genetic susceptibility or hyperoxic stress to perturb this complicated process can cause abnormal enlargement of alveoli and lead to bronchopulmonary dysplasia (BPD)-associated emphysema. Plateletderived growth factor receptor α (PDGFRα) signaling is crucial for alveolar myofibroblast (MYF) proliferation and its deficiency is associated with risk of BPD, but posttranscriptional mechanisms regulating PDGFRα synthesis during lung development remain largely unexplored. Cytoplasmic polyadenylation element-binding protein 2 (CPEB2) is a sequence-specific RNA-binding protein and translational regulator. Because CPEB2-knockout (KO) mice showed emphysematous phenotypes, we investigated how CPEB2-controlled translation affects pulmonary development and function. Methods: Respiratory and pulmonary functions were measured by whole-body and invasive plethysmography. Histological staining and immunohistochemistry were used to analyze morphology, proliferation, apoptosis and cell densities from postnatal to adult lungs. Western blotting, RNA-immunoprecipitation, reporter assay, primary MYF culture and ectopic expression rescue were performed to demonstrate the role of CPEB2 in PDGFRα mRNA translation and MYF proliferation. Results: Adult CPEB2-KO mice showed emphysema-like dysfunction. The alveolar structure in CPEB2-deficient lungs appeared normal at birth but became simplified through the alveolar stage of lung development. In CPEB2-null mice, we found reduced proliferation of MYF progenitors during alveolarization, abnormal deposition of elastin and failure of alveolar septum formation, thereby leading to enlarged pulmonary alveoli. We identified that CPEB2 promoted PDGFRα mRNA translation in MYF progenitors and this positive regulation could be disrupted by H 2 O 2 , a hyperoxia-mimetic treatment. Moreover, decreased proliferating ability in KO MYFs due to insufficient PDGFRα expression was rescued by ectopic expression of CPEB2, suggesting an important role of CPEB2 in upregulating PDGFRα signaling for pulmonary alveologenesis. Conclusions: CPEB2-controlled translation, in part through promoting PDGFRα expression, is indispensable for lung development and function. Since defective pulmonary PDGFR signaling is a key feature of human BPD, CPEB2 may be a risk factor for BPD.

show abstract

“…3b). miR - 34 - 5p plays critical role in several biological processes such as cell proliferation48, cell differentiation49, and cell cycle progression50. miR - 34 - 5p also regulates nervous system development in vertebrates and in the fruit fly5152.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-34 directly targets pair-rule genes and cytoskeleton component in the honey bee

Freitas

Pires

Claudianos

et al. 2017

Sci Rep

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are key regulators of developmental processes, such as cell fate determination and differentiation. Previous studies showed Dicer knockdown in honeybee embryos disrupt the processing of functional mature miRNAs and impairs embryo patterning. Here we investigated the expression profiles of miRNAs in honeybee embryogenesis and the role of the highly conserved miR-34-5p in the regulation of genes involved in insect segmentation. A total of 221 miRNAs were expressed in honey bee embryogenesis among which 97 mature miRNA sequences have not been observed before. Interestingly, we observed a switch in dominance between the 5-prime and 3-prime arm of some miRNAs in different embryonic stages; however, most miRNAs present one dominant arm across all stages of embryogenesis. Our genome-wide analysis of putative miRNA-target networks and functional pathways indicates miR-34-5p is one of the most conserved and connected miRNAs associated with the regulation of genes involved in embryonic patterning and development. In addition, we experimentally validated that miR-34-5p directly interacts to regulatory elements in the 3′-untranslated regions of pair-rule (even-skipped, hairy, fushi-tarazu transcription factor 1) and cytoskeleton (actin5C) genes. Our study suggests that miR-34-5p may regulate the expression of pair-rule and cytoskeleton genes during early development and control insect segmentation.

show abstract

miRNA‐34a promotes proliferation of human pulmonary artery smooth muscle cells by targeting PDGFRA

Cited by 58 publications

References 46 publications

MiRNAs in β-Cell Development, Identity, and Disease

MiRNAs in β-Cell Development, Identity, and Disease

CPEB2-activated PDGFRα mRNA translation contributes to myofibroblast proliferation and pulmonary alveologenesis

MicroRNA-34 directly targets pair-rule genes and cytoskeleton component in the honey bee

Contact Info

Product

Resources

About