Regulation of ion transport by microRNAs

Elvira-Matelot, Emilie; Jeunemaı̂tre, Xavier; Hadchouel, Juliette

doi:10.1097/mnh.0b013e328348b4aa

Cited by 11 publications

(9 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, microRNAs (miRNAs) emerged as a major class of gene expression regulators implicated in deregulation of ion channel genes leading to channelopathies [9] . The consequence of miRNAs in fine-tuning gene expression shows that changes in the abundance of a single miRNA can affect the levels of expression of several different functional proteins [10, 11] .…”

Section: Introductionmentioning

confidence: 99%

MicroRNA 16 modulates epithelial sodium channel in human alveolar epithelial cells

Parthasarathy

Galam

Huynh

et al. 2012

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Acute lung injury (ALI) is a devastating disease characterized by pulmonary edema. Removal of edema from the air spaces is a critical function of the epithelial sodium channel (ENaC) in ALI. The molecular mechanisms behind resolution of pulmonary edema are incompletely understood. MicroRNA’s (miRNA) are crucial gene regulators and are dysregulated in various diseases including ALI. Recent studies suggest that microRNA-16 (miR-16) targets serotonin transporter (SERT) involved in the serotonin (5-HT) transmitter system. Alterations in serotonin levels have been reported in various pulmonary diseases. However, the role of miR-16 on its target SERT, and ENaC, a key ion channel involved in the resolution of pulmonary edema, have not been studied. In the present study, the expression patterns of miR-16, SERT, ENaC and serotonin were investigated in mice exposed to room air and hyperoxia. The effects of miR-16 overexpression on ENaC, SERT, TGF-β and Nedd4 in human alveolar epithelial cells were analyzed. miR-16 and ENaC were downregulated in mice exposed to hyperoxia. miR-16 downregulation in mouse lung was correlated with an increase in SERT expression and pulmonary edema. Overexpression of miR-16 in human alveolar epithelial cells (A549) suppressed SERT and increased ENaCβ levels when compared to control-vector transfected cells. In addition, miR-16 over expression suppressed TGFβ release, a critical inhibitor of ENaC. Interestingly Nedd4, a negative regulator of ENaC remained unaltered in miR-16 over expressed A549 cells when compared to controls. Taken together, our data suggests that miR-16 upregulates ENaC, a major sodium channel involved in resolution of pulmonary edema in ALI.

show abstract

Section: Introductionmentioning

confidence: 99%

MicroRNA 16 modulates epithelial sodium channel in human alveolar epithelial cells

Parthasarathy

Galam

Huynh

et al. 2012

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

show abstract

“…We further demonstrated in vivo and in vitro that renal miR-200b (or miR-200b-3p) and miR-717 were tonicity-responsive and that their down-regulation contributed significantly to hypertonicity-induced induction of osmoregulatory transcription factor nuclear factor of activated T cell-5/osmotic response element binding protein/tonicity responsive element binding protein (Nfat5/OREBP/TonEBP) [4,8,16,19]. These findings firmly established the essential roles of miR-200b-3p and miR-717 in renal osmoregulation and homeostasis [5,14,15,44]. However, the roles of many other tonicity-responsive miRNAs, in particular those that appeared to be regulated in an opposite direction as compared with that of miR-200b-3p and miR-717 in vitro (i.e., up-regulated rather than down-regulated following the 2-h hypertonicity exposure), were largely uncharacterized and remained to be further investigated.…”

Section: Introductionmentioning

confidence: 65%

Sfmbt2 10th intron-hosted miR-466(a/e)-3p are important epigenetic regulators of Nfat5 signaling, osmoregulation and urine concentration in mice

Luo

Liu

et al. 2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

View full text Add to dashboard Cite

Sfmbt2-hosted miR-466a-3p and its close relatives are often among the most significantly up-regulated or down-regulated miRNAs in responses to numerous deleterious environmental stimuli. The exact roles of these miRNAs in cellular stress responses, however, are not clear. Here we showed that many Sfmbt2-hosted miRNAs were highly hypertonic stress responsive in vitro and in vivo. In renal medulla, water deprivation induced alterations in the expression of miR-466(a/b/c/e/p)-3p in a pattern similar to that of miR-200b-3p, a known regulator of osmoresponsive transcription factor Nfat5. Remarkably, exposure of mIMCD3 cells to an arginine vasopressin analog time-dependently down-regulated the expression of miR-466(a/b/c/e/p)-3p and miR-200b-3p, which provides a novel regulatory mechanism for these osmoresponsive miRNAs. In cultured mIMCD3 cells we further demonstrated that miR-466a-3p and miR-466g were capable of targeting Nfat5 by interacting with its 3'UTR. In transgenic mice overexpressing miR-466a-3p, significant down-regulation of Nfat5 and many other osmoregulation-related genes was observed in both the renal cortex and medulla. Moreover, sustained transgenic over-expression of miR-466a-3p was found to be associated with polydipsia, polyuria and disturbed ion homeostasis and kidney morphology. Since the mature sequence of miR-466a-3p is completely equivalent to that of miR-466e-3p and that the seed sequence of miR-466a-3p is completely equivalent to that of miR-297(a/b/c)-3p, miR-466d-3p, miR-467g and miR-669d-3p, and that miR-466a-3p differs from miR-466(b/c/p)-3p only in a 5' nucleotide, we propose that miR-466a-3p and many of its close relatives are important epigenetic regulators of renal Nfat5 signaling, osmoregulation and urine concentration in mice.

show abstract

“…miRs are a class of endogenous and conserved small RNA molecules (~22 nt) that play gene regulatory roles in targeting mRNAs for cleavage or translational repression [17]. Based on the finding of the recent studies, miRs are found to have a pivotal role in the regulation of fluid and electrolyte balance [18,19]. It warrants further investigation to identify tonicity-inducible miRs and to determine their potential roles in osmoregulatory responses.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of MicroRNA-messenger RNA interactome in ex-vivo gill filaments, Anguilla japonica

Nong

et al. 2020

BMC Genomics

View full text Add to dashboard Cite

Background: Gills of euryhaline fishes possess great physiological and structural plasticity to adapt to large changes in external osmolality and to participate in ion uptake/excretion, which is essential for the re-establishment of fluid and electrolyte homeostasis. The osmoregulatory plasticity of gills provides an excellent model to study the role of microRNAs (miRs) in adaptive osmotic responses. The present study is to characterize an ex-vivo gill filament culture and using omics approach, to decipher the interaction between tonicity-responsive miRs and gene targets, in orchestrating the osmotic stress-induced responses. Results: Ex-vivo gill filament culture was exposed to Leibovitz's L-15 medium (300 mOsmol l − 1 ) or the medium with an adjusted osmolality of 600 mOsmol l − 1 for 4, 8 and 24 h. Hypertonic responsive genes, including osmotic stress transcriptional factor, Na + /Cl − -taurine transporter, Na + /H + exchange regulatory cofactor, cystic fibrosis transmembrane regulator, inward rectifying K + channel, Na + /K + -ATPase, and calcium-transporting ATPase were significantly upregulated, while the hypo-osmotic gene, V-type proton ATPase was downregulated. The data illustrated that the ex-vivo gill filament culture exhibited distinctive responses to hyperosmotic challenge. In the hyperosmotic treatment, four key factors (i.e. drosha RNase III endonuclease, exportin-5, dicer ribonuclease III and argonaute-2) involved in miR biogenesis were dysregulated (P < 0.05). Transcriptome and miR-sequencing of gill filament samples at 4 and 8 h were conducted and two downregulated miRs, miR-29b-3p and miR-200b-3p were identified. An inhibition of miR-29b-3p and miR-200b-3p in primary gill cell culture led to an upregulation of 100 and 93 gene transcripts, respectively. Commonly upregulated gene transcripts from the hyperosmotic experiments and miR-inhibition studies, were overlaid, in which two miR-29b-3p target-genes [Krueppel-like factor 4 (klf4), Homeobox protein Meis2] and one miR-200b-3p target-gene (slc17a5) were identified. Integrated miR-mRNA-omics analysis revealed the specific binding of miR-29b-3p on Klf4 and miR-200b-3p on slc17a5. The target-genes are known to regulate differentiation of gill ionocytes and cellular osmolality.(Continued on next page) Conclusions: In this study, we have characterized the hypo-osmoregulatory responses and unraveled the modulation of miR-biogenesis factors/the dysregulation of miRs, using ex-vivo gill filament culture. MicroRNAmessenger RNA interactome analysis of miR-29b-3p and miR-200b-3p revealed the gene targets are essential for osmotic stress responses.

show abstract

Regulation of ion transport by microRNAs

Cited by 11 publications

References 48 publications

MicroRNA 16 modulates epithelial sodium channel in human alveolar epithelial cells

MicroRNA 16 modulates epithelial sodium channel in human alveolar epithelial cells

Sfmbt2 10th intron-hosted miR-466(a/e)-3p are important epigenetic regulators of Nfat5 signaling, osmoregulation and urine concentration in mice

Genome-wide analysis of MicroRNA-messenger RNA interactome in ex-vivo gill filaments, Anguilla japonica

Contact Info

Product

Resources

About