MicroRNA-30a as a candidate underlying sex-specific differences in neonatal hyperoxic lung injury: implications for BPD

Zhang, Yuhao; Coarfa, Cristian; Dong, Xiaoyu; Jiang, Weiwu; Hayward-Piatkovskyi, Brielle; Gleghorn, Jason P.; Lingappan, Krithika

doi:10.1152/ajplung.00372.2018

Cited by 38 publications

(30 citation statements)

References 76 publications

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“…After hyperoxia exposure, miR-30a-3p and -5p levels increased significantly in female mice lungs on postnatal days 7 and 21 [27]. Similarly, in neonatal human pulmonary microvascular endothelial cells exposed to hyperoxia, samples obtained from females expressed significantly higher levels of miR-30a-3p and -5p compared to levels in male samples [27]. Altogether, there were significant decreases in miR-30a-3p and -5p levels, and increased mRNA and protein levels of DLL4 in human BPD lung samples.…”

Section: Consequences Of Mirnas Expression In the Developing Lungmentioning

confidence: 97%

“…The administration of miR-876-3p mimic to postnatal day 14 mice exposed to hyperoxia restored alveolar structures and reduced neutrophilic inflammation [26]. After hyperoxia exposure, miR-30a-3p and -5p levels increased significantly in female mice lungs on postnatal days 7 and 21 [27]. Similarly, in neonatal human pulmonary microvascular endothelial cells exposed to hyperoxia, samples obtained from females expressed significantly higher levels of miR-30a-3p and -5p compared to levels in male samples [27].…”

Section: Consequences Of Mirnas Expression In the Developing Lungmentioning

confidence: 97%

“…Altogether, there were significant decreases in miR-30a-3p and -5p levels, and increased mRNA and protein levels of DLL4 in human BPD lung samples. [27]. In another set of experiments carried in newborn mice, hyperoxia disrupted alveolar architecture and the injection of an inhibitor for miR-421 attenuated the process [28].…”

Section: Consequences Of Mirnas Expression In the Developing Lungmentioning

confidence: 98%

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miRNAs in Lung Development and Diseases

Boateng

Krauss‐Etschmann

2020

IJMS

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The development of the lung involves a diverse group of molecules that regulate cellular processes, organ formation, and maturation. The various stages of lung development are marked by accumulation of small RNAs that promote or repress underlying mechanisms, depending on the physiological environment in utero and postnatally. To some extent, the pathogenesis of various lung diseases is regulated by small RNAs. In this review, we discussed miRNAs regulation of lung development and diseases, that is, COPD, asthma, pulmonary fibrosis, and pulmonary arterial hypertension, and also highlighted possible connotations for human lung health.After fertilization in the mouse, total miRNA in the two-cell-stage embryo was demonstrated to be significantly lower than the levels in one-cell zygote [15]. Notably, total miRNA in the four-cell-stage embryo was higher than the levels in the two-cell-stage embryo [15]. In the early mouse embryo, miR-127 was upregulated at E6.5 and E7.5 [16]. Overexpression of miR-127 in mouse embryonic stem cells, which differentiated into embryoid bodies, increased the mRNA levels of Gsc, Foxa2, and Brachyury (mesendoderm markers), but elicited no change in Pax6 and Otx2 (ectoderm markers) three days after transfection. Inhibition of miR-127 showed opposite regulation of Gsc, Foxa2, and Brachyury. miR-127, moreover, was suggested to control mesendoderm differentiation [16]. miR-326 regulated sonic hedgehog signaling by targeting Smo and Gli2 [17]. The inhibition of smoothened in cultured explanted E12 mouse lung resulted in the expansion of distal epithelium, and disruption of normal branching pattern and mesenchymal integrity [17]. Another study described the functional role of miR-142-3p in the mouse embryonic lung mesenchyme. The miRNA was shown to regulate adenomatous polyposis coli to further modulate Wnt signaling [18]. Taken together, miR-142-3p regulated the proliferation and differentiation of mesenchymal progenitors in the mouse embryonic lung [18].In the developing mouse lung, the level of miR-17 was stable (E11.5-E16.5), predominantly at the pseudoglandular stage, with higher epithelial levels at E12.5 [19]. Simultaneous knockdown of miR-17 and its paralogs, miR-20a and miR-106b, for 72 h in epithelial lung explants altered branching, even in FGF10-treated condition [19]. In the human fetal lung, miR-449a was upregulated at 18-20 weeks (canalicular stage), and in the mouse embryonic lung, miR-449a level was increased from E15.5 to E18.5 [20]. The inhibition of miR-449a in E16.5 mouse lung culture (end of pseudoglandular stage) increased the mRNA levels of Mycn and Sox9, and the protein levels of Ki-67 and SOX9 particularly in the distal epithelial region [20].Knockout of miR-26a-1/miR-26a-2 in the mouse promoted the formation of dilated lumens and aerated regions at the beginning of the canalicular stage (E16.5) of lung development [21]. Results at the saccular stage (E18.5) also indicated large lamellar bodies, and increased SP-A, SP-B, and SP-C protein levels in miR-26a knockout mice....

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Section: Consequences Of Mirnas Expression In the Developing Lungmentioning

confidence: 97%

Section: Consequences Of Mirnas Expression In the Developing Lungmentioning

confidence: 97%

Section: Consequences Of Mirnas Expression In the Developing Lungmentioning

confidence: 98%

See 1 more Smart Citation

miRNAs in Lung Development and Diseases

Boateng

Krauss‐Etschmann

2020

IJMS

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“…We have previously shown that alveolarization and pulmonary angiogenesis is preserved in hyperoxia-exposed female neonatal mice compared to males [8]. The protective effect in females is accompanied by an increase in pulmonary miR-30a expression in females [9]. miR-30a has proangiogenic, anti-inflammatory, and antifibrotic effects in many diseases processes [10–17], including those affecting the lung.…”

Section: Introductionmentioning

confidence: 99%

Role of HIF-1α-miR30a-Snai1 Axis in Neonatal Hyperoxic Lung Injury

Zhang

Dong

Lingappan

2019

Oxidative Medicine and Cellular Longevity

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Bronchopulmonary dysplasia (BPD) is characterized by a severe impairment in lung alveolarization and vascular development. We have previously shown that pulmonary angiogenesis is preserved in hyperoxia-exposed female mice accompanied by increased miR-30a expression, which is a proangiogenic miRNA. Also, miR-30a expression is decreased in human BPD. HIF-1α plays an essential role in postnatal lung development, especially in recovery from hyperoxic injury. Snai1 activation promotes pathological fibrosis through many mechanisms including Endo-MT, which may in turn adversely impact lung vascular development. Our objective was to test the hypothesis that higher miR-30a expression through HIF-1α decreases Snai1 expression in females and attenuates injury in the developing lung. Neonatal male and female mice (C57BL/6) were exposed to hyperoxia (P1-5, 0.95 FiO2) and euthanized on P21. Neonatal human pulmonary microvascular endothelial cells (HPMECs; 18-24-week gestation donors; 3/group either sex) were subjected to hyperoxia (95% O2 and 5% CO2) or normoxia (air and 5% CO2) up to 72 h. Snai1 expression was measured in HPMECs in vitro and in neonatal mouse lungs in vivo. Also, Snai1 expression was measured in HPMECs after miR-30a mimic and miR-30a inhibitor treatment. To further establish the potential regulation of miR-30a by Hif-1α, miR-30a expression after Hif-1α inhibition was measured in HPMECs. In vivo, Snai1 expression was decreased in neonatal female lungs compared to males at P7. Increased Snai1 expression was seen in male HPMECs upon exposure to hyperoxia in vitro. Treatment with the miR-30a mimic decreased Snai1 expression in HPMECs, while miR-30a inhibition significantly increased Snai1 expression in HPMECs. siRNA-mediated loss of Hif-1α expression in HPMECs decreased miR-30a expression. Hif-1α may lead to differential sex-specific miR-30a expression and may contribute to protection from hyperoxic lung injury in female neonatal mice through decreased Snai1 expression.

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“…Donor sex alone has been found to influence phenotype in pulmonary microvascular endothelial cells. 268 , 269 Since hormones can heavily influence immune and lung function, it is important to account for the presence of hormones in media. 29 , 223 Phenol red-free media is recommended for such studies because phenol red can interact with estrogen receptors.…”

Section: Opportunities For Bioengineers To Study Respiratory Viral LImentioning

confidence: 99%

Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Progression

et al. 2020

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COVID-19 is a disease that manifests itself in a multitude of ways across a wide range of tissues. Many factors are involved, and though impressive strides have been made in studying this novel disease in a very short time, there is still a great deal that is unknown about how the virus functions. Clinical data has been crucial for providing information on COVID-19 progression and determining risk factors. However, the mechanisms leading to the multi-tissue pathology are yet to be fully established. Although insights from SARS-CoV-1 and MERS-CoV have been valuable, it is clear that SARS-CoV-2 is different and merits its own extensive studies. In this review, we highlight unresolved questions surrounding this virus including the temporal immune dynamics, infection of non-pulmonary tissue, early life exposure, and the role of circadian rhythms. Risk factors such as sex and exposure to pollutants are also explored followed by a discussion of ways in which bioengineering approaches can be employed to help understand COVID-19. The use of sophisticated in vitro models can be employed to interrogate intercellular interactions and also to tease apart effects of the virus itself from the resulting immune response. Additionally, spatiotemporal information can be gleaned from these models to learn more about the dynamics of the virus and COVID-19 progression. Application of advanced tissue and organ system models into COVID-19 research can result in more nuanced insight into the mechanisms underlying this condition and elucidate strategies to combat its effects.

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MicroRNA-30a as a candidate underlying sex-specific differences in neonatal hyperoxic lung injury: implications for BPD

Cited by 38 publications

References 76 publications

miRNAs in Lung Development and Diseases

miRNAs in Lung Development and Diseases

Role of HIF-1α-miR30a-Snai1 Axis in Neonatal Hyperoxic Lung Injury

Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Progression

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