SGK1 regulation by miR-466g in cortical collecting duct cells

Jacobs, Mollie E.; Kathpalia, Paru P.; Chen, Yu; Thomas, Sydney F.; Noonan, Emily J.; Pao, Alan C.

doi:10.1152/ajprenal.00024.2016

Cited by 14 publications

(12 citation statements)

References 43 publications

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“…There is currently little information about miRs and Na + regulation. Direct regulation of ENaC function by miRs was demonstrated by our group, and in a recent study the regulation of the serum glucocorticoid kinase (SGK1) was demonstrated to be altered by aldosterone‐regulated miRs (Edinger et al, ; Jacobs et al, ). These studies suggest that miRs are capable of acting as intermediary components in the aldosterone signaling cascade (Edinger et al, ).…”

Section: Discussionmentioning

confidence: 90%

“…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: 90%

mentioning

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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“…82 Another miR-466 isoform (not part of this cluster), miR-466g was also shown to target SGK1. 83 As miRs-466a/e & b/c were upregulated after a 24-hours aldosterone stimulation, our focus shifted to the miR-466 F I G U R E 6 Heatmap of % of miRs predicted to bind to the mRNAs listed (from miRDB predictions). The higher the number of miRs shared between the targets, the darker the square.…”

Section: Discussionmentioning

confidence: 99%

Aldosterone‐induced microRNAs act as feedback regulators of mineralocorticoid receptor signaling in kidney epithelia

et al. 2020

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The final steps in the Renin‐Angiotensin‐Aldosterone signaling System (RAAS) involve binding of the corticosteroid hormone, aldosterone to its mineralocorticoid receptor (MR). The bound MR interacts with response elements to induce or repress the transcription of aldosterone‐regulated genes. A well characterized aldosterone‐induced gene is the serum and glucocorticoid‐induced kinase (SGK1), which acts downstream to increase sodium transport in distal kidney nephron epithelial cells. The role of microRNAs (miRs) induced by extended aldosterone stimulation in regulating MR and SGK1 has not been reported. In these studies, miRs predicted to bind to the 3ʹ‐UTR of mouse MR were profiled by qRT‐PCR after aldosterone stimulation. The miR‐466a/b/c/e family was upregulated in mouse kidney cortical collecting duct epithelial cells. A luciferase reporter assay confirmed miR‐466 binding to both MR and SGK1 3ʹ‐UTRs. Inhibition of miR‐466 increased MR and SGK1 mRNA and protein levels. Inhibiting miR‐466b and preventing its upregulation after aldosterone stimulation increased amiloride‐sensitive sodium transport and sensitivity to aldosterone stimulation. In vivo upregulation of miR‐466 was confirmed in distal nephrons of mice on low Na+ diets. Repression of MR and SGK1 by aldosterone‐induced miRs may represent a negative feedback loop that contributes to a form of aldosterone escape in vivo.

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“…Furthermore, mimic miR-27a/b was verified to bind to the 3′-UTR of intersectin-2 to depress endocytosis of ENaC proteins. miR-466g, as a novel aldosterone responsive molecule, regulated ENaC activity in CCD cells probably through the glucocorticoid regulated kinase 1 pathway [ 46 ]. These miRs reinforced an important role for miRs as a new element in the renin–angiotensin–aldosterone system signaling cascade that maintains Na + transport in the kidney ( Fig.…”

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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SGK1 regulation by miR-466g in cortical collecting duct cells

Abstract: Jacobs ME, Kathpalia PP, Chen Y, Thomas SV, Noonan EJ, Pao AC. SGK1 regulation by miR-466g in cortical collecting duct cells.

Cited by 14 publications

References 43 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

Aldosterone‐induced microRNAs act as feedback regulators of mineralocorticoid receptor signaling in kidney epithelia

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

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