MicroRNA-7-5p regulates human alveolar epithelial sodium channels by targeting the mTORC2/SGK-1 signaling pathway

Qin, Ke; Zhong, Xi; Wang, Daoxin

doi:10.1080/01902148.2016.1197347

Cited by 13 publications

(13 citation statements)

References 30 publications

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“…These studies suggest that miRs are capable of acting as intermediary components in the aldosterone signaling cascade (Edinger et al, ). Direct regulation of ENaC by miRs has been reported for miR‐16 (Tamarapu Parthasarathy et al, ) and miR‐7 (Qin et al, ) in alveolar epithelial cells and regulation of miR‐101 and ‐199 by ENaC in endometrial cells (Sun et al, ). Neither of these reports focused on miR regulation by hormones, and none of these ENaC‐targeting miRs were significantly altered in response to aldosterone in our microarray assays.…”

Section: Discussionmentioning

confidence: 97%

“…miRs also play a significant role in kidney maintenance and normal kidney physiology (Sequeira‐Lopez et al, ; Mladinov et al, ). Recent evidence suggests that miRs may be important intermediaries in the hormonal signaling cascades that alter ion transport in both the airway (Qi et al, ; Qin et al, ) and the kidney (Elvira‐Matelot et al, ; Sober et al, ; Robertson et al, ; Edinger et al, ; Butterworth, ; Jacobs et al, ).…”

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confidence: 99%

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A MicroRNA Cluster miR‐23–24–27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport

Liu

Edinger

Klemens

et al. 2017

Journal Cellular Physiology

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The epithelial sodium channel (ENaC) is expressed in the epithelial cells of the distal convoluted tubules, connecting tubules, and cortical collecting duct (CCD) in the kidney nephron. Under the regulation of the steroid hormone aldosterone, ENaC is a major determinant of sodium (Na+) and water balance. The ability of aldosterone to regulate microRNAs (miRs) in the kidney has recently been realized, but the role of miRs in Na+ regulation has not been well established. Here we demonstrate that expression of a miR cluster mmu-miR-23–24–27, is upregulated in the CCD by aldosterone stimulation both in vitro and in vivo. Increasing the expression of these miRs increased Na+ transport in the absence of aldosterone stimulation. Potential miR targets were evaluated and miR-27a/b was verified to bind to the 3′-untranslated region of intersectin-2, a multi-domain protein expressed in the distal kidney nephron and involved in the regulation of membrane trafficking. Expression of Itsn2 mRNA and protein was decreased after aldosterone stimulation. Depletion of Itsn2 expression, mimicking aldosterone regulation, increased ENaC-mediated Na+ transport, while Itsn2 overexpression reduced ENaC’s function. These findings reinforce a role for miRs in aldosterone regulation of Na+ transport, and implicate miR-27 in aldosterone’s action via a novel target.

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

A MicroRNA Cluster miR‐23–24–27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport

Liu

Edinger

Klemens

et al. 2017

Journal Cellular Physiology

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“…MiRs are a category of non-coding single-stranded RNA segments that are encoded by endogenous genes [ 12 ]. Through complete or incomplete pairing with the complementary sequences of 3′-UTR of targeting mRNAs, miRs degrade the 3′-UTR chain or interrupt translation [ 15 , 16 ]. Apparently, miRs regulate both transcriptional and translational processes either by increasing mRNA degradation or inhibiting protein translation [ 17 , 18 ], and thus negatively alter the synthesis of the corresponding proteins and ultimately regulating multiple cellular activities [ 19 – 22 ].…”

Section: Biogenesis and Nomenclature Of Mirsmentioning

confidence: 99%

“…2) A549 epithelial cells have some characteristics of authentic alveolar epithelial type 2 cells and when challenged by LPS, there was a reduction in the expression of miR-7-5p restored the expression of αβγ ENaC protein via silencing both the target of rapamycin and glucocorticoid regulated kinase 1 genes. It may be feasible that ENaC expression and function could be benefited by a reduction in miR-7-5p expression [ 15 ]. 3) Although diverse results had been reported, there was a significant decrease in lung β ENaC in hyperoxic mice compared to normoxic controls.…”

Section: Inter-regulation Of Mirs and Enacs In Normal And Diseased Timentioning

confidence: 99%

ENaCs as Both Effectors and Regulators of MiRNAs in Lung Epithelial Development and Regeneration

Ding

Zhao

et al. 2017

Cell Physiol Biochem

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Epithelial sodium channels (ENaC) play an important role in re-absorbing excessive luminal fluid by building up an osmotic Na⁺ gradient across the tight epithelium in the airway, the lung, the kidney, and the colon. The ENaC is a major pathway for retention of salt in kidney too. MicroRNAs (miRs), a group of non-coding RNAs that regulate gene expression at the post-transcriptional level, have emerged as a novel class of regulators for ENaC. Given the ENaC pathway is crucial for maintaining fluid homeostasis in the lung and the kidney and other cavities, we summarized the cross-talk between ENaC and miRs and recapitulated the underlying regulatory factors, including aldosterone, transforming growth factor-β1, and vascular endothelial growth factor-A in the lung and other epithelial tissues/organs. We have compared the profiling of miRs between normal and injured mice and human lungs, which showed a significant alteration in numerous miRs in mouse models of LPS and ventilator induced ARDS. In addition, we reiterated the potential regulation of the ENaC by miRs in stem/ progenitor cell-based re-epithelialization, and identified a promising pharmaceutic target of ENaC for removing edema fluid in ARDS by mesenchymal stem cells-released paracrine. In conclusion, it seems that the interactions between miRs and scnn1s/ENaCs are critical for lung development, epithelial cell turnover in adult lungs, and re-epithelialization for repair.

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“…MSCs release multiple microRNAs (miRNAs) into conditioned medium, which may involve in the benefits of MSCs in re-alveolarization during MSC-induced reparative processes of injured respiratory epithelium in injured lungs [15]. This feature can regulate the permeability of endothelium and epithelium, participate in inflammatory response, increase AFC, repair tissue damage, and exert various biological functions [16,17].…”

Section: Introductionmentioning

confidence: 99%

Conditioned Medium of Bone Marrow Mesenchymal Stem Cells Relieves Acute Lung Injury in Mice by Regulating Epithelial Sodium Channels via miR-34c

Zhou¹,

Cui

Hou³

et al. 2020

Preprint

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Aims: One of the characteristics of acute lung injury (ALI) is severe pulmonary edema, which is closelyrelated to alveolar fluid clearance. Mesenchymal stem cells (MSCs) secrete a wide range of cytokines,growth factors and miRNAs through paracrine action to participate in the mechanism of pulmonaryinflammatory response, which increases the clearance of edema fluid, and promotes the repair process ofALI. However, the mechanism by which bone marrow derived MSCs-conditioned medium (BMSCs-CM)promotes edema clearance is unclear. Epithelial sodium channel (ENaC) is the rate-limiting step in thesodium-water transport and edema clearance in the alveolar cavity, and we aim to explore the role of ENaCin BMSCs-CM invloved edema clearance and whether it can alter the function of ENaC via miRNAs.Methods: CCK-8 cell proliferation assay was used to detect the effect of BMSCs-CM on the survival ofAT2 cells. Real-time PCR (RT-PCR) and Western blot were used to detect the expression of ENaC in AT2cells. The effects of exosomes/miR-34c on the transepithelial short-circuit current in the monolayer of H441cells were examined by the Ussing chamber setup. Dual luciferase reporter gene assay was used to detect thetarget gene of miR-34c.Results: BMSCs-CM can increase the viability of mouse AT2 cells. RT-PCR and Western blotting resultsshowed that BMSCs-CM significantly increased the expression of γ-ENaC subunit in mouse AT2 cells.Ussing chamber assay revealed that BMSCs-CM enhanced the amiloride-sensitive currents associated withENaC activity in intact H441 cell monolayers. In addition, we observed higher expression of miR-34c inmouse AT2 cells administrated with BMSCs-CM, and the overexpression or inhibition of miR-34c canregulate the expression of ENaC protein and alter the function of ENaC. Finally, we detected MARCKS maybe one of the target gene of miR-34c.Conclusions: Our results indicate that BMSCs-CM may improve LPS-induced ALI through miR-34ctargeting MARCKS and regulating ENaC indirectly, which further explores the benefit of paracrine effectsof BMSCs on edematous ALI.

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MicroRNA-7-5p regulates human alveolar epithelial sodium channels by targeting the mTORC2/SGK-1 signaling pathway

Abstract: Our results demonstrate that miRNA-7-5p can regulate the expression of human alveolar ENaC by targeting the mTORC2/SGK-1 signaling pathway. The inhibition of miRNA-7-5p can enhance the expression of ENaC, which may provide a new target for the treatment of ARDS.

Cited by 13 publications

References 30 publications

A MicroRNA Cluster miR‐23–24–27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport

A MicroRNA Cluster miR‐23–24–27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport

ENaCs as Both Effectors and Regulators of MiRNAs in Lung Epithelial Development and Regeneration

Conditioned Medium of Bone Marrow Mesenchymal Stem Cells Relieves Acute Lung Injury in Mice by Regulating Epithelial Sodium Channels via miR-34c

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MicroRNA-7-5p regulates human alveolar epithelial sodium channels by targeting the mTORC2/SGK-1 signaling pathway

Abstract: Our results demonstrate that miRNA-7-5p can regulate the expression of human alveolar ENaC by targeting the mTORC2/SGK-1 signaling pathway. The inhibition of miRNA-7-5p can enhance the expression of ENaC, which may provide a new target for the treatment of ARDS.

Cited by 13 publications

References 30 publications

A MicroRNA Cluster miR‐23–24–27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport

A MicroRNA Cluster miR‐23–24–27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport

ENaCs as Both Effectors and Regulators of MiRNAs in Lung Epithelial Development and Regeneration

Conditioned Medium of Bone Marrow Mesenchymal Stem Cells Relieves Acute Lung Injury in Mice by Regulating Epithelial Sodium Channels via&nbsp;miR-34c

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Conditioned Medium of Bone Marrow Mesenchymal Stem Cells Relieves Acute Lung Injury in Mice by Regulating Epithelial Sodium Channels via miR-34c