Mice carrying ubiquitin-specific protease 2 (<i>Usp2</i>) gene inactivation maintain normal sodium balance and blood pressure

Pouly, Daniel; Debonneville, Anne; Ruffieux-Daidié, Dorothée; Maillard, Marc; Abriel, Hugues; Loffing, Johannes; Staub, Olivier

doi:10.1152/ajprenal.00012.2013

Cited by 28 publications

(33 citation statements)

References 57 publications

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“…To investigate if a similar regulation occurs in principal cells of the collecting duct in vivo, mice of both sexes were placed on low sodium diets to induce aldosterone signaling, as we and others have done previously (Nesterov et al, ; Pouly et al, ; Edinger et al, ). Kidneys were harvested and CCD cells isolated.…”

Section: Resultsmentioning

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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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: Resultsmentioning

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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“…These proteins likely work in concert with the ubiquitin ligase Nedd4-2 that is involved in the endocytic pathway. No evidence supports a limiting role of these proteins for the aldosterone effect on ENaC, because mouse models with complete knockout of the genes encoding these proteins (Nedd4-2, SGK, USP2-45, GILZ) failed to suppress the response of ENaC-mediated renal Na + absorption to aldosterone (Fejes-Toth et al, 2008;Suarez et al, 2012;Pouly et al, 2013;Ronzaud et al, 2013). The complete picture of the aldosterone signaling pathway that controls ENaCmediated Na + absorption remains therefore largely unknown.…”

Section: B Epithelial Na + Channelmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCI. Structure, Function, and Pharmacology of Acid-Sensing Ion Channels and the Epithelial Na⁺Channel

2014

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“…Since Cyclin D1 is one of the important known substrates of the USP2 for controlling cell proliferation [23], we hypothesized that USP2 contributes to the osteoblast The nucleotide sequences of the primers are indicated in the supplemental Table 1 . 4a) and in the primary osteoblasts (Fig.…”

Section: Pth1-34 Treatment Did Not Increase Cyclind1 Protein Level Inmentioning

confidence: 99%

“…Previous studies investigating the effects of PTH1-34 on cultured osteoblastic cells indicated that the ubiquitin-specific peptidase 2 (Usp2, also named as Ubp41) may be one of the direct target genes of PTHR signaling [22]. Usp2 is a cytoplasmic molecule harboring deubiquitinase activity and is expressed in various cell types [23,24]. Importantly, it has been indicated that PTH1R is one of the deubiquitination targets of the Usp2 [25], in addition to the cellcycle regulatory molecules such as CyclinD1, MDM2, and MDM4 [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

PTH-Induced Osteoblast Proliferation Requires Upregulation of the Ubiquitin-Specific Peptidase 2 (Usp2) Expression

et al. 2015

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Osteoporosis is a common disease that increases individual's fragility fracture risk. PTH is the only therapeutic agent for severe osteoporosis that requires anabolic action of bone formation. Although a part of the PTH actions is explained by increased proliferation of osteoblastic precursor cells, the mechanisms involved in the proliferation of osteoblastic cells by PTH have not been clarified yet. Therefore, in this study, we investigated the effects of PTH on gene expression in the cultured osteoblastic MC3T3-E1 cells, and found that the ubiquitin-specific peptidase 2 (Usp2) may be one of the direct target genes of PTHR signaling. Usp2 is a deubiquitination enzyme targeting various factors including CyclinD1 in cancer cells and PTH receptor 1 in osteoblasts. We confirmed that consistent induction of Usp2 expression peaked at 1 h by PTH1-34 (teriparatide) in MC3T3-E1 cells and primary calvarial osteoblasts. Among the three known splicing variants of the Usp2, we found the isoforms 1 and 2 are predominantly expressed in osteoblasts. Live-imaging analysis of the Fucci-transgenic mouse-derived primary osteoblasts indeed demonstrated that Usp2 is required for the PTH1-34-induced osteoblast proliferation. Western blotting analysis of the CyclinD1 indicated that Usp2 knock-down influences the paradoxical changes of CyclinD1 protein levels in this condition. Our data indicate that Usp2 is required for the PTH1-34-induced proliferation of osteoblasts.

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Mice carrying ubiquitin-specific protease 2 (Usp2) gene inactivation maintain normal sodium balance and blood pressure

Cited by 28 publications

References 57 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

International Union of Basic and Clinical Pharmacology. XCI. Structure, Function, and Pharmacology of Acid-Sensing Ion Channels and the Epithelial Na⁺Channel

PTH-Induced Osteoblast Proliferation Requires Upregulation of the Ubiquitin-Specific Peptidase 2 (Usp2) Expression

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Mice carrying ubiquitin-specific protease 2 (Usp2) gene inactivation maintain normal sodium balance and blood pressure

Cited by 28 publications

References 57 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

International Union of Basic and Clinical Pharmacology. XCI. Structure, Function, and Pharmacology of Acid-Sensing Ion Channels and the Epithelial Na+Channel

PTH-Induced Osteoblast Proliferation Requires Upregulation of the Ubiquitin-Specific Peptidase 2 (Usp2) Expression

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International Union of Basic and Clinical Pharmacology. XCI. Structure, Function, and Pharmacology of Acid-Sensing Ion Channels and the Epithelial Na⁺Channel