The long non-coding RNA MEG8 induces an endothelial barrier through regulation of microRNA-370 and -494 processing

Kremer, Veerle; Stanicek, Laura; Ingen, Eva van; Bink, Diewertje I.; Hilderink, Sarah; Tijsen, Anke J.; Wittig, Ilka; Mägdefessel, Lars; Nossent, A. Yaël; Boon, Reinier A.

doi:10.1242/jcs.259671

Cited by 4 publications

(2 citation statements)

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“…Recent literature has investigated the role of lncRNAs in endothelial function and identified lncRNA MEG8 as a positive regulator of angiogenic sprouting and proliferation (Kremer, Bink et al., 2022 ; Kremer, Stanicek et al., 2022 ). Also, lncRNA Aerrie beneficially controls angiogenesis, migration and barrier integrity, and is an important regulator of DNA damage repair (Pham et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Higher gestational weight gain delays wound healing and reduces expression of long non‐coding RNA KLRK1‐AS1 in neonatal endothelial progenitor cells

Weiss,

Schrüfer,

Tocantins

et al. 2023

The Journal of Physiology

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High gestational weight gain (GWG) is a cardiovascular risk factor and may disturb neonatal endothelial function. Long non‐coding RNAs (lncRNAs) regulate gene expression epigenetically and can modulate endothelial function. Endothelial colony forming cells (ECFCs), circulating endothelial precursors, are a recruitable source of endothelial cells and sustain endothelial function, vascular growth and repair. We here investigated whether higher GWG affects neonatal ECFC function and elucidated the role of lncRNAs herein. Wound healing of umbilical cord blood‐derived ECFCs after pregnancies with GWG <13 kg versus >13 kg was determined in a scratch assay and based on monolayer impedance after electric wounding (electric cell‐substrate impedance sensing, ECIS). LncRNA expression was analysed by RNA sequencing. The function of killer cell lectin‐like receptor K1 antisense RNA (KLRK1‐AS1) was investigated after siRNA‐based knockdown. Closure of the scratch was delayed by 25% (P = 0.041) in the higher GWG group and correlated inversely with GWG (R = −0.538, P = 0.012) in all subjects (n = 22). Similarly, recovery of the monolayer barrier after electric wounding was delayed (−11% after 20 h; P = 0.014; n = 15). Several lncRNAs correlated with maternal GWG, the most significant one being KLRK1‐AS1 (log2 fold change = −0.135, P < 0.001, n = 35). KLRK1‐AS1 knockdown (n = 4) reduced barrier recovery after electric wounding by 21% (P = 0.029) and KLRK1‐AS1 expression correlated with the time required for wound healing for both scratch (R = 0.447, P = 0.033) and impedance‐based assay (R = 0.629, P = 0.014). Higher GWG reduces wound healing of neonatal ECFCs, and lower levels of the lncRNA KLRK1‐AS1 may underlie this. imageKey points Maternal cardiovascular risk factors such as diabetes, obesity and smoking in pregnancy disturb fetal endothelial function, and we here investigated whether also high gestational weight gain (GWG) has an impact on fetal endothelial cells. Circulating endothelial progenitor cells (endothelial colony forming cells, ECFCs) are highly abundant in the neonatal blood stream and serve as a circulating pool for vascular growth and repair. We revealed that higher GWG delays wound healing capacity of ECFCs in vitro. We identified the regulatory RNA lncRNA KLRK1‐AS1 as a link between GWG and delayed ECFC wound healing. Our data show that high GWG, independent of pre‐pregnancy BMI, affects neonatal ECFC function.

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Section: Discussionmentioning

confidence: 99%

Higher gestational weight gain delays wound healing and reduces expression of long non‐coding RNA KLRK1‐AS1 in neonatal endothelial progenitor cells

Weiss,

Schrüfer,

Tocantins

et al. 2023

The Journal of Physiology

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“…In HUVECs, the levels of maternally expressed gene 8 (MEG8) lncRNA increased with passage number, suggesting its upregulation with aging. Its knockdown slightly increased senescence and impaired the endothelial barrier, indicating a protective role for this lncRNA in vascular aging [79]. Opa-interacting protein 5 antisense RNA 1 (Oip5-AS1) levels were increased in the aortas of aged mice.…”

Section: Cardiovascular Diseasesmentioning

confidence: 99%

The Impact of Long Noncoding RNAs in Tissue Regeneration and Senescence

Tavares e Silva,

Pessoa,

Nóbrega-Pereira

et al. 2024

Cells

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Overcoming senescence with tissue engineering has a promising impact on multiple diseases. Here, we provide an overview of recent studies in which cellular senescence was inhibited through the up/downregulation of specific lncRNAs. This approach prevented senescence in the bones, joints, nervous system, heart, and blood vessels, with a potential impact on regeneration and the prevention of osteoarthritis and osteoporosis, as well as neurodegenerative and cardiovascular diseases. Senescence of the skin and liver could also be prevented through the regulation of cellular levels of specific lncRNAs, resulting in the rejuvenation of cells from these organs and their potential protection from disease. From these exciting achievements, which support tissue regeneration and are not restricted to stem cells, we propose lncRNA regulation through RNA or gene therapies as a prospective preventive and therapeutic approach against aging and multiple aging-related diseases.

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